System and method for regulating cardiopulmonary triggered therapy to the brain

ABSTRACT

A medical device system includes a brain monitoring element, cardiopulmonary monitoring element, therapy module and a processor. The processor is configured to activate the therapy module upon detection of a cardiopulmonary event in the cardiopulmonary signal. The processor is further configured to monitor the brain signal and communicate to the therapy module to change the cardiopulmonary triggered therapeutic output to the brain based upon the brain monitoring. Methods of treating a person with a neurological disorder are also provided.

RELATED APPLICATION

This application claims priority to provisional U.S. Application Ser.No. 60/636,929, filed Dec. 17, 2004 which is incorporated by reference.

FIELD OF THE INVENTION

This invention relates generally to medical devices, and moreparticularly to the improved monitoring of cardiopulmonary signals todetect and diagnose neurological events and to provide therapy toprevent or terminate neurological events.

BACKGROUND OF THE INVENTION

Nervous system disorders affect millions of people, causing death and adegradation of life. Nervous system disorders include disorders of thecentral nervous system, peripheral nervous system, and mental health andpsychiatric disorders. Such disorders include, for example withoutlimitation, epilepsy, Parkinson's disease, essential tremor, dystonia,and multiple sclerosis (MS). Additionally, nervous system disordersinclude mental health disorders and psychiatric disorders which alsoaffect millions of individuals and include, but are not limited to,anxiety (such as general anxiety disorder, panic disorder, phobias, posttraumatic stress disorder (PTSD), and obsessive compulsive disorder(OCD)), mood disorders (such as major depression, bipolar depression,and dysthymic disorder), sleep disorders (narcolepsy), eating disorderssuch as obesity, and anorexia. The term “neurological disorder” issynonymous with “nervous system disorder” herein. As an example of anervous system disorder, epilepsy is the most prevalent seriousneurological disease across all ages. Epilepsy is a group ofneurological conditions in which a person has or is predisposed torecurrent seizures. A seizure is a clinical manifestation resulting fromexcessive, hypersynchronous, abnormal electrical or neuronal activity inthe brain. A neurological event is an activity that is indicative of anervous system disorder. A seizure is a type of a neurological event.This electrical excitability of the brain may be likened to anintermittent electrical overload that manifests with sudden, recurrent,and transient changes of mental function, sensations, perceptions, orinvoluntary body movement. Because the seizures are unpredictable,epilepsy affects a person's employability, psychosocial life, andability to operate vehicles or power equipment. It is a disorder thatoccurs in all age groups, socioeconomic classes, cultures, andcountries.

There are various approaches to treating nervous system disorders.Treatment therapies can include any number of possible modalities aloneor in combination including, for example, electrical stimulation,magnetic stimulation, drug infusion, or brain temperature control. Eachof these treatment modalities may use open loop treatment where neitherthe timing of the therapy nor treatment parameters are automatically setor revised based on information coming from a sensed signal. Each ofthese treatment modalities may also be operated using closed-loopfeedback control. Such closed-loop feedback control techniques mayreceive from a monitoring element a brain signal (such as EEG, ECoG,intracranial pressure, change in quantity of neurotransmitters) thatcarries information about a symptom or a condition of a nervous systemdisorder and is obtained from the head or brain of the patient.

For example, U.S. Pat. No. 5,995,868 discloses a system for theprediction, rapid detection, warning, prevention, or control of changesin activity states in the brain of a patient. Use of such a closed-loopfeed back system for treatment of a nervous system disorder may providesignificant advantages in that treatment can be delivered before theonset of the symptoms of the nervous system disorder.

Efficacy of treatment of nervous system disorders depends upon not onlythe therapy applied but also the timing of the application of thetherapy. Therefore, the accuracy and timeliness of the detectionalgorithm and system affects the efficacy of the therapy. It istherefore desirable to develop better detection schemes and algorithmsthat are more accurate or are able to provide earlier detection.

One nervous system disorder that may be considered a subset of theepilepsy disease is sudden unexpected death in epilepsy, or SUDEP, isdefined as sudden, unexpected, often unwitnessed, non-traumatic andnon-drowning death in patients for which no cause has been found exceptfor the individual having a history of seizures. Depending on the cohortstudied, SUDEP is responsible for 2% to 18% of all deaths in patientswith epilepsy, and the incidence may be up to 40 times higher in youngadults with epilepsy than among persons without seizures.

Although the pathophysiological mechanisms leading to death are notfully understood, experimental, autopsy and clinical evidence implicateseizure related heart and pulmonary dysfunction or indicators. Pulmonaryevents may include obstructive sleep apnea (OSA), central apnea, andneurogenic pulmonary edema. Cardiac events may include cardiacarrhythmic abnormalities including sinus arrhythmia, sinus pause,premature atrial contraction (PAC), premature ventricular contraction(PVC), irregular rhythm (wandering pacemaker, multifocal atrialtachycardia, atrial fibrillation), asystole or paroxysmal tachycardia.Cardiac events may also include conduction abnormalities includingAV-block (AVB) and bundle branch block (BBB) and repolarizationabnormalities including T-wave inversion and ST-elevation or depression.Lastly, hypertension, hypotension and vaso-vagal syncope (VVS) arecommon in epilepsy patients.

Specific risk factors also play a part in sudden death in epilepsy—ie,age (young), gender (male), poor seizure control, nocturnal seizures,severity and quantity of seizures, poor compliance with medicants,alcohol or drug use, and stress.

Epileptic seizures are associated with autonomic neuronal dysfunctionthat result in a broad array of abnormalities of cardiac and pulmonaryfunction. Different pathophysiological events may contribute to SUDEP indifferent patients, and the mechanism is probably multifactorial.Without intervention, respiratory events, including airway obstruction,central apnea and neurogenic pulmonary edema are probably terminalevents. In addition, cardiac arrhythmia and anomalies, during the ictaland interictal periods, leading to arrest and acute cardiac failure alsoplays an important role in potentially terminal events. For example, thepaper “Electrocardiographic Changes at Seizure Onset”, Leutmezer, et al,Epilepsia 44(3): 348-354, 2003 describes cardiovascular anomalies, suchas heart rate variability (HRV), tachycardia and bradycardia, that mayprecede, occur simultaneous or lag behind EEG seizure onset. “CardiacAsystole in Epilepsy: Clinical and Neurophysiologic Features”, Rocamora,et al, Epilepsia 44(2): 179-185, 2003 reports that cardiac asystole is“provoked” by the seizure. “Electrocardiograph QT Lengthening Associatedwith Epileptiform EEG Discharges—a Role in Sudden Unexplained Death inEpilepsy”, Tavernor, et al, Seizure 5(1): 79-83, March 1996 reports QTlengthening during seizures in SUDEP patients versus control. “Effectsof Seizures on Autonomic and Cardiovascular Function”, Devinsky EpilepsyCurrents 4(2): 43-46, March/April 2004 describes ST segment depressionand T-wave inversion, AVB, VPC and BBB during or immediately after aseizure. “Sudden Unexplained Death in Children with Epilepsy”, Donner,et al, Neurology 57: 430-434, 2001 reports that bradycardia isfrequently preceded by hypoventilation or apnea suggesting that heartrate changes during seizures may be a result of cardiorespiratoryreflexes. Lastly, “EEG and ECG in Sudden Unexplained Death in Epilepsy”,Nei, et al, Epilepsia 45(4) 338-345, 2004 reports on sinus tachycardiaduring or after seizures.

Obstructive sleep apnea is often associated with epilepsy and SUDEP atrisk patients. OSA is typically treated with continuous positive airwaypressure (CPAP), oral appliances, surgery, positional therapy or weightloss. These often are not totally successful or device (CPAP orappliance) compliance is low.

With the above broad and, often conflicting, array of neurocardiopulmonary physiological anomalies, manifestations and indicators,a flexible multi-programmable device, or array of flexiblemulti-programmable devices, is desired to allow for better diagnosis,monitoring and treatment of nervous system disorders.

SUMMARY OF THE INVENTION

A medical device system for initiating therapy to the brain for aneurological disorder based on activity in the cardiopulmonary system.In one embodiment of the invention, a medical device system is providedthat includes a brain monitoring element, respiratory monitoringelement, therapy module and a processor. The processor is configured toactivate the therapy module upon detection of a respiratory event in therespiratory signal. The processor is further configured to monitor thebrain signal and communicate to the therapy module to change thetherapeutic output to the brain based upon the brain monitoring. Methodsof treating a person with a neurological disorder using cardiopulmonarysignals are also provided.

BRIEF DESCRIPTION OF THE DRAWINGS

Core Monitor

FIG. 1 is a simplified schematic view of a thoracic cavity leadlessmedical device implanted in a patient that monitors cardiac andrespiratory parameters relating to a nervous system disorder.

FIG. 2 is a simplified schematic view of an alternative embodimentcardiac leaded medical device implanted in a patient that monitorscardiac and respiratory parameters relating to nervous system disorder.

FIG. 3 is a simplified schematic view of an alternative embodimentsensor stub medical device implanted in a patient that monitors cardiacand respiratory parameters relating to nervous system disorder.

FIG. 4 is a simplified schematic view of an alternative embodimentexternal patch medical device used by a patient that monitors cardiacand respiratory parameters relating to nervous system disorder.

Full Monitor

FIG. 5 is a simplified schematic view of an alternative embodimentthoracic leadless and cranial leaded medical device implanted in apatient that monitors cardiac, respiratory and brain parameters relatingto nervous system disorder.

FIG. 6 is a simplified schematic view of an alternative embodimentcardiac and cranial leaded medical device implanted in a patient thatmonitors cardiac, respiratory and brain parameters relating to nervoussystem disorder.

FIG. 7 is a simplified schematic view of an alternative embodimentsensor stub and cranial leaded medical device implanted in a patientthat monitors cardiac, respiratory and brain parameters relating tonervous system disorder.

FIG. 8 is a simplified schematic view of an alternative embodimentexternal patch and cranial leaded medical device implanted in a patientthat monitors cardiac, respiratory and brain parameters relating tonervous system disorder.

FIG. 9 is a simplified schematic view of an alternative embodimentintegrated brain lead medical device implanted in a patient thatmonitors cardiac, respiratory and brain parameters relating to nervoussystem disorder.

FIG. 10 is a simplified schematic view of an alternative embodimentcranial implant medical device implanted in a patient that monitorscardiac and brain parameters relating to nervous system disorder.

Monitor+Treatment (Brain)

FIG. 11 is a simplified schematic view of an alternative embodimentthoracic leadless and cranial leaded medical device implanted in apatient that monitors cardiac, respiratory and brain parameters relatingto nervous system disorders and provides brain treatment.

FIG. 12A is a simplified schematic view of an alternative embodimentcardiac and cranial leaded medical device implanted in a patient thatmonitors cardiac, respiratory and brain parameters relating to nervoussystem disorders and provides brain treatment.

FIG. 12B is a simplified schematic view of an alternative embodimentcardiac and cranial leaded medical device implanted in a patient thatmonitors cardiac, respiratory and brain parameters relating to nervoussystem disorders and provides brain treatment.

FIG. 13 is a simplified schematic view of an alternative embodimentsensor stub and cranial leaded medical device implanted in a patientthat monitors cardiac, respiratory and brain parameters relating tonervous system disorders and provides brain treatment.

FIG. 14 is a simplified schematic view of an alternative embodimentexternal patch and cranial leaded medical device implanted in a patientthat monitors cardiac, respiratory and brain parameters relating tonervous system disorders and provides brain treatment.

FIG. 15 is a simplified schematic view of an alternative embodimentintegrated brain lead medical device implanted in a patient thatmonitors cardiac, respiratory and brain parameters relating to nervoussystem disorders and provides brain treatment.

FIG. 20 is a simplified schematic view of an alternative embodimentthoracic leadless device to cranial implant via wireless connect medicaldevice implanted in a patient that monitors cardiac, respiratory andbrain parameters relating to nervous system disorders and provides braintreatment.

FIG. 21 is a simplified schematic view of an alternative embodimentexternal patch to cranial implant via wireless connect medical deviceimplanted in a patient that monitors cardiac, respiratory and brainparameters relating to nervous system disorders and provides braintreatment.

Monitor+Treatment (Brain+Respiration)

FIG. 16A is a simplified schematic view of an alternative embodimentcardiac, brain and phrenic nerve leaded medical device implanted in apatient that monitors cardiac, respiratory and brain parameters relatingto nervous system disorders and provides brain and respirationtreatment.

FIG. 16B is a simplified schematic view of an alternative embodimentcardiac, brain and phrenic nerve leaded medical device implanted in apatient that monitors cardiac, respiratory and brain parameters relatingto nervous system disorders and provides brain and respirationtreatment.

FIG. 17 is a simplified schematic view of an alternative embodimentsensor stub, brain and phrenic nerve leaded medical device implanted ina patient that monitors cardiac, respiratory and brain parametersrelating to nervous system disorders and provides brain and respirationtreatment.

FIG. 18 is a simplified schematic view of an alternative embodimentintegrated brain and phrenic nerve leaded medical device implanted in apatient that monitors cardiac, respiratory and brain parameters relatingto nervous system disorders and provides brain and respirationtreatment.

FIG. 19 is a simplified schematic view of an alternative embodimentbrain and integrated respiration lead medical device implanted in apatient that monitors cardiac, respiratory and brain parameters relatingto nervous system disorders and provides brain and respirationtreatment.

Monitor+Treatment (Brain+Cardiac)

FIG. 24A is a simplified schematic view of an alternative embodimentcardiac and brain leaded medical device implanted in a patient thatmonitors cardiac, respiratory and brain parameters relating to nervoussystem disorders and provides brain and cardiac treatment.

FIG. 24B is a simplified schematic view of an alternative embodimentcardiac and brain leaded medical device implanted in a patient thatmonitors cardiac, respiratory and brain parameters relating to nervoussystem disorders and provides brain and cardiac treatment.

FIG. 22 is a simplified schematic view of an alternative embodimentcranial implant to defibrillator vest via wireless connect medicaldevice used by a patient that monitors cardiac, respiratory and brainparameters relating to nervous system disorders and provides brain andcardiac treatment.

FIG. 23 is a simplified schematic view of an alternative embodimentcranial implant to leadless defibrillator (lifeboat) via wirelessconnect medical device used by a patient that monitors cardiac,respiratory and brain parameters relating to nervous system disordersand provides brain and cardiac treatment.

Monitor+Treatment (Brain+Respiration+Cardiac)

FIG. 25A is a simplified schematic view of an alternative embodimentcardiac, cranial and phrenic nerve leaded medical device implanted in apatient that monitors cardiac, respiratory and brain parameters relatingto nervous system disorders and provides brain and respiration andcardiac treatment.

FIG. 25B is a simplified schematic view of an alternative embodimentcardiac, cranial and phrenic nerve leaded medical device implanted in apatient that monitors cardiac, respiratory and brain parameters relatingto nervous system disorder and provides brain and respiration andcardiac treatment.

Detailed Design

FIG. 26 is a simplified block diagram of a core monitor as shown in FIG.1 above.

FIG. 27 is a graphical representation of the signals sensed by coremonitor as shown in FIG. 1 above.

FIG. 28 is a simplified block diagram of a core monitor as shown in FIG.2 above.

FIG. 29 is a simplified block diagram of a core monitor as shown in FIG.3 above.

FIG. 30 is a simplified block diagram of a core monitor as shown in FIG.4 above.

FIG. 31 is a flow diagram showing operation of a core monitor as shownin FIG. 1-4 above.

FIG. 32 is a simplified block diagram of a full monitor as shown in FIG.5 above.

FIG. 33 is a simplified block diagram of a full monitor as shown in FIG.6 above.

FIG. 34 is a simplified block diagram of a full monitor as shown inFIGS. 7 and 9 above.

FIG. 35 is a simplified block diagram of a full monitor as shown in FIG.8 above.

FIG. 36 is a simplified block diagram of a full monitor as shown in FIG.10 above.

FIG. 37 is a flow diagram showing operation of a full monitor as shownin FIG. 5-10 above.

FIG. 38 is a diagram of exemplary physiologic data from a patient with afull monitor as shown in relation to FIG. 5-10 above.

FIG. 39 shows a process for identifying ECG and respiratoryabnormalities recorded during detected seizures in a full monitor asshown in relation to FIG. 5-10 above.

FIG. 40A shows a process for enabling the cardiac or respiratorydetectors for neurological event detection in a full monitor as shown inrelation to FIG. 5-10 above and detection/treatment as described in FIG.41-51 below.

FIG. 40B shows a process for enabling the ECG or respiratory detectorsfor seizure detection in a full monitor as shown in relation to FIG.5-10 above and detection/treatment as described in FIG. 41-51 below.

FIG. 41 is a simplified block diagram of a full monitor with brainstimulation therapy as shown in FIG. 11 above.

FIG. 42 is a simplified block diagram of a full monitor with brainstimulation therapy as shown in FIG. 12A above.

FIG. 43 is a simplified block diagram of a full monitor with brainstimulation therapy as shown in FIG. 12B above.

FIG. 44 is a simplified block diagram of a full monitor with brainstimulation therapy as shown in FIGS. 13 and 15 above.

FIG. 45 is a simplified block diagram of a full monitor with brainstimulation therapy as shown in FIG. 14 above.

FIG. 46 is a simplified block diagram of a full monitor with brainstimulation therapy as shown in FIG. 20 above.

FIG. 47 is a simplified block diagram of a full monitor with brainstimulation therapy as shown in FIG. 21 above.

FIG. 48 is a simplified block diagram of a full monitor with brain andrespiration stimulation therapy as shown in FIG. 16A above.

FIG. 49 is a simplified block diagram of a full monitor with brain andrespiration stimulation therapy as shown in FIG. 16B above.

FIG. 50 is a simplified block diagram of a full monitor with brain andrespiration stimulation therapy as shown in FIGS. 17, 18 and 19 above.

FIG. 51 is a simplified block diagram of a full monitor with brain andcardiac stimulation therapy as shown in FIG. 24A above.

FIG. 52 is a simplified block diagram of a full monitor with brain andcardiac stimulation therapy as shown in FIG. 24B above.

FIG. 53 is a simplified block diagram of a full monitor with brain andcardiac stimulation therapy as shown in FIGS. 22 and 23 above.

FIG. 54 is a simplified block diagram of a full monitor with brain,respiration and cardiac stimulation therapy as shown in FIG. 25A above.

FIG. 55 is a simplified block diagram of a full monitor with brain,respiration and cardiac stimulation therapy as shown in FIG. 25B above.

FIG. 56 is a flow diagram showing operation of a full monitor withtherapy (including brain, respiration or cardiac stimulation therapy) asshown in FIG. 11-25 above.

FIG. 57A is a flow diagram showing a process for enablingcardiac/respiratory detectors for neurological event detection andtreatment including termination rules.

FIG. 57B is a flow diagram showing a process for enablingECG/respiratory detectors for seizure detection and treatment includingtermination rules.

FIG. 58 is a schematic diagram of a system utilizing any of theabove-described embodiments and allowing remote monitoring anddiagnostic evaluation of at risk patients.

FIG. 59 is a schematic diagram of an alternative system utilizing any ofthe above-described embodiments and allowing remote monitoring anddiagnostic evaluation of at risk patients.

DETAILED DESCRIPTION OF THE INVENTION

The term “cardiopulmonary monitoring element” used herein means anydevice, component or sensor that receives a physiologic signalindicative of heart activity or respiratory activity or both and outputsa cardiopulmonary signal that is based upon the sensed physiologicsignal(s). Some examples of a cardiopulmonary monitoring element includeleads, electrodes, chemical sensors, biological sensors, pressuresensors, and temperature sensors. A monitoring element does not have tobe located in the heart or lungs to be a cardiopulmonary monitoringelement. The term cardiopulmonary monitoring element is not the same asthe term “monitor” also used herein, although a cardiopulmonarymonitoring element could be a part of a monitor.

The term “brain monitoring element” used herein means any device,component or sensor that receives a physiologic signal from the brain orhead of a patient and outputs a brain signal that is based upon thesensed physiologic signal. Some examples of a brain monitoring elementinclude leads, electrodes, chemical sensors, biological sensors,pressure sensors, and temperature sensors. A monitoring element does nothave to be located in the brain to be a brain monitoring element. Theterm brain monitoring element is not the same as the term “monitor” alsoused herein, although a brain monitoring element could be a part of amonitor.

The term “cardiac monitoring element” used herein means any device,component or sensor that receives or infers a physiological signal fromthe heart of a patient and outputs a cardiac signal that is based uponsensed physiologic signal. Some examples of cardiac monitoring elementsinclude leads, electrodes, chemical sensors, biological sensor, pressuresensors and temperature sensors. A monitoring element does not have tobe located in the heart or adjacent to the heart to be a cardiacmonitoring element. For example, a sensor or electrode adapted forsensing a cardiac signal and placed on the housing of an implantabledevice is a cardiac monitoring element. Furthermore, a cardiacmonitoring element could be an externally placed sensor such as a holtermonitoring system. The term “cardiac monitoring element” is not the sameas the term “monitor” also used herein although a cardiac monitoringelement could be a part of a monitor. A cardiac monitoring element isone embodiment of a cardiopulmonary monitoring element.

The term “respiratory monitoring element” used herein means any device,component or sensor that receives a physiologic signal indicative ofactivity or conditions in the lungs of a patient and outputs arespiration signal that is based upon the sensed physiologic signal.Some examples of respiration monitoring elements are provided below. Amonitoring element does not have to be located in the lungs or adjacentto the lungs to be a respiratory monitoring element. The term“respiratory monitoring element” is not the same as the term “monitor”also used herein although a respiratory monitoring element could be apart of a monitor. A respiratory monitoring element is one embodiment ofa cardiopulmonary monitoring element.

It is noted that many embodiments of the invention may reside on anyhardware embodiment currently understood or conceived in the future.Many example hardware embodiments are provided in this specification.These examples are not meant to be limiting of the invention.

Core Monitor

Cardiopulmonary monitoring in the Core Monitor device (as describedbelow in more detail in conjunction with FIGS. 1-4 and 26-30) monitorscardiac (e.g., ECG, blood pressure) or respiration signals or bothcontinuously and may record these signals in a loop recorder eitherautomatically or manually when the patient indicates they have had aneurological event such as a seizure. “Cardiopulmonary system” meansheart activity, respiratory activity or both. “Cardiopulmonary signal”means (i) a cardiac signal; or (ii) a respiratory signal; or (iii) botha cardiac signal and a respiratory signal. “Cardiopulmonary monitoring”means monitoring (i) cardiac activity; or (ii) respiratory activity; or(iii) both. “Cardiopulmonary event” means a cardiac or respiratory event(or both) indicative of some physiological change (e.g., medicalcondition, disturbance, abnormality, pattern) in the cardiac orrespiratory signals. Real-time analysis of the cardiac signal evaluatesrate disturbances (e.g., bradycardia; tachycardia; asystole) as well asany indications of cardiac ischemia (e.g., ST segment changes; T waveinversion, etc.). Real-time analysis of the respiration signal evaluatesrespiration disturbances (e.g., respiration rate, minute ventilation,apnea, prolonged pauses).

Abnormalities detected during real-time analysis will lead to animmediate patient alert. This alert can be audible (beeps, buzzers,tones, spoken voice, etc.), light, tactile, or other means.

Automatic loop recording may save the data for a programmable period oftime. For example, the device may be programmed to save a period of timebefore a cardiac detection (e.g., 30 seconds of ECG raw or processeddata before detection) and a second period of time after the detection(e.g., 3 minutes of ECG raw or processed data after detection).

The medical device system may also include a manual activation mode inwhich the patient provides an indication (e.g., push a button on aholter, patient programmer or other external patient activator device)when a neurological event is occurring or has just occurred. In manualactivation mode, to allow for the fact that the patient may not mark theneurological event until the neurological event has ended, the ECG looprecording may begin a longer time period before the event is marked. Forexample, the medical device system may save ECG data beginning 15minutes before the patient mark. This time period may be programmable.Post-processing of this saved signal will analyze the data to evaluateheart rate changes during the neurological event, heart rate variabilityand changes in ECG waveforms. Manual patient indication of aneurological event will be done through the patient external activatordevice 22. The patient (or caregiver) will push a button on the externaldevice, while communicating with the implanted device. This will providea marker and will initiate a loop recording. In addition, prolonged ECGloop recordings are possible (e.g., in the case of SUDEP, recording alldata during sleep since the incidence of SUDEP is highest in patientsduring sleep).

Post-processing of the signal can occur in the implanted device, thepatient's external device or in the clinician external device.Intermittently (e.g., every morning, once/week, following a neurologicalevent), the patient may download data from the implantable device to thepatient external device. This data will then be analyzed by the externaldevice (or sent through a network to the physician) to assess any ECG orrespiratory abnormalities. If an abnormality is detected, the devicewill notify the patient/caregiver. At that time, the patient/caregiveror device can inform the healthcare provider of the alert to allow afull assessment of the abnormality. The clinician external device isalso capable of obtaining the data from the implanted device andconducting an analysis of the stored signals. If a potentiallylife-threatening abnormality is detected, the appropriate medicaltreatment can be prescribed (e.g., cardiac abnormality: a pacemaker, animplantable defibrillator, or a heart resynchronization device may beindicated or respiration abnormality: CPAP, patient positioning, orstimulation of respiration may be indicated).

FIG. 1 is a simplified schematic view of one embodiment of a coreMonitor 100 implanted in a patient 10. Monitor 100 continuously sensesand monitors the cardiac and respiration function of patient 10 via oneor more monitoring elements 14 (e.g., cardiac electrodes) to allowdetection of neurological events, the recording of data and signals preand post event. Stored diagnostic data is uplinked and evaluated by thepatient's physician utilizing programmer 12 via a 2-way telemetry link32. An external patient activator 22 may optionally allow the patient10, or other care provider (not shown), to manually activate therecording of diagnostic data.

Monitor 100, as stated above, typically includes one or more monitoringelements 14 such as several subcutaneous spiral electrodes that areembedded individually into three or four recessed casings placed in acompliant surround that is attached to the perimeter of implantedmonitor 100 as substantially described in U.S. Pat. No. 6,512,940“Subcutaneous Spiral Electrode for Sensing Electrical Signals of theHeart” to Brabec, et al and U.S. Pat. No. 6,522,915 “Surround ShroudConnector and Electrode Housings for a Subcutaneous Electrode Array andLeadless ECGS” to Ceballos, et al. These electrodes are electricallyconnected to the circuitry of the implanted Monitor 100 to allow thedetection of cardiac depolarization waveforms (as substantiallydescribed in U.S. Pat. No. 6,505,067 “System and Method for Deriving aVirtual ECG or EGM Signal” to Lee, et al.) that may be further processedto detect cardiac electrical characteristics (e.g., heart rate, heartrate variability, arrhythmias, cardiac arrest, sinus arrest and sinustachycardia). Further processing of the cardiac signal amplitudes may beused to detect respiration characteristics (e.g., respiration rate,minute ventilation, and apnea).

To aid in the implantation of Monitor 100 in a proper position andorientation, an implant aid may be used to allow the implantingphysician to determine the proper location/orientation as substantiallydescribed in U.S. Pat. No. 6,496,715 “System and Method for NoninvasiveDetermination of Optimal Orientation of an Implantable Sensing Device”to Lee, et al.

FIG. 2 is a simplified schematic view of a second embodiment coreMonitor 120 implanted in a patient 10. Monitor 120 continuously sensesand monitors cardiac and respiration function of patient 10 via cardiaclead(s) 16 to allow detection of neurological events and the recordingof data and signals pre and post event. Stored diagnostic data isuplinked and evaluated by the patient's physician utilizing programmer12 via a 2-way telemetry link 32. An external patient activator 22 mayoptionally allow the patient 10, or other care provider (not shown), tomanually activate the recording of diagnostic data. Monitor 120 sensesboth cardiac signals and respiration parameters via standard cardiacleads implanted in the heart. Monitor 120 measures intra-cardiacimpedance, varying both with the intrathoracic pressure fluctuationsduring respiration and with cardiac contraction is representative of thepulmonary activity and of the cardiac activity as substantiallydescribed in U.S. Pat. No. 5,003,976 “Cardiac and PulmonaryPhysiological Analysis via Intracardiac Measurements with a SingleSensor” to Alt. Cardiac leads 16 may consist of any typical leadconfiguration as is known in the art, such as, without limitation, rightventricular (RV) pacing or defibrillation leads, right atrial (RA)pacing or defibrillation leads, single pass RA/RV pacing ordefibrillation leads, coronary sinus (CS) pacing or defibrillationleads, left ventricular pacing or defibrillation leads, pacing ordefibrillation epicardial leads, subcutaneous defibrillation leads,unipolar or bipolar lead configurations, or any combinations of theabove lead systems.

FIG. 3 is a simplified schematic view of a third embodiment core Monitor140 implanted in a patient 10. Monitor 140 continuously senses andmonitors cardiac and respiration function of patient 10 via an electrode(not shown) located distally on sensor stub 20 which is insertedsubcutaneously in the thoracic area of the patient to allow detection ofneurological events and the recording of data and signals pre and postevent. Stored diagnostic data is uplinked and evaluated by the patient'sphysician utilizing programmer 12 via a 2-way telemetry link 32. Anexternal patient activator 22 may optionally allow the patient 10, orother care provider (not shown), to manually activate the recording ofdiagnostic data. Monitor 140 senses cardiac signals between an electrodeon the distal end of the sensor stub and the monitor case as describedin conjunction with the embodiment shown in FIG. 5 in U.S. Pat. No.5,987,352 “Minimally Invasive Implantable Device for MonitoringPhysiologic Events” to Klein, et al. Monitor 140 also senses respirationparameters such as respiration rate, minute ventilation and apnea viameasuring and analyzing the impedance variations measured from theimplanted monitor 140 case to the electrode (not shown) located distallyon sensor stub lead 20 as substantially described in U.S. Pat. No.4,567,892 “Implantable Cardiac Pacemaker” and U.S. Pat. No. 4,596,251“Minute Ventilation Dependent Rate Responsive Pacer” both to Plicchi, etal.

FIG. 4 is a simplified schematic view of a fourth embodiment coreMonitor 160 attached to a patient 10. External patch Monitor 160continuously senses and monitors cardiac and respiration function ofpatient 10 to allow detection of neurological events and the recordingof data and signals pre and post event. Stored diagnostic data isuplinked and evaluated by the patient's physician utilizing programmer12 via a 2-way telemetry link 32. An external patient activator 22 mayoptionally allow the patient 10, or other care provider (not shown), tomanually activate the recording of diagnostic data. Also optionally, abutton 38 on the external patch monitor 160 may be activated by thepatient 10 to manually activate diagnostic data recording.

External patch Monitor 160 consists of a resilient substrate affixed tothe patient's skin with the use of an adhesive which provides supportfor an amplifier, memory, microprocessor, receiver, transmitter andother electronic components as substantially described in U.S. Pat. No.6,200,265 “Peripheral Memory Patch and Access Method for Use With anImplantable Medical Device” to Walsh, et al. The substrate flexes in acomplimentary manner in response to a patient's body movements providingpatient comfort and wearability. The low profile external patch Monitor160 is preferably similar in size and shape to a standard bandage, andmay be attached to the patient's skin in an inconspicuous location.Uplinking of stored physiologic telemetry data from the internal memoryof external patch Monitor 160 may be employed to transfer informationbetween the monitor and programmer 12.

Full Monitor

The term “full monitor” is used to describe a monitor that is capable ofmonitoring the brain (such as by monitoring a brain signal such as anelectroencephalogram (EEG)) and additionally the cardiopulmonary system.Monitoring of the brain and cardiopulmonary system will allow the fullmonitor to collect neurological signals and at least one of thecardiovascular and respiratory signals in close proximity toneurological events detected (such as seizures) as well as notifying thepatient/caregiver of a prolonged neurological event (such as statusepilepticus). Cardiopulmonary monitoring may occur around a neurologicalevent (in the case of a seizure this is called peri-ictal). Indistinction from the core monitor, in which patients/caregivers mustnotify the device that a neurological event has occurred, the fullmonitor device will detect the neurological event (based on the brainsignal) and will automatically analyze the peri-ictal signals andinitiate the loop recording. Monitoring of more than one physiologicsignal allows for greater understanding of the total physiologiccondition of the patient. For example, prolonged or generalized seizuresput patients at higher risk for SUDEP, the EEG monitoring may beprogrammed to provide alerts when a neurological event has exceeded apre-determined duration or severity.

FIG. 5 is a simplified schematic view of a full Monitor 200 implanted ina patient 10. Monitor 200 continuously senses and monitors cardiac,brain and respiration function of patient 10 via one or more brainmonitoring elements 18 and one or more cardiac monitoring elements 14 orone or more respiratory monitoring elements 15. Brain monitoringelements 18 may be for example, one or more brain leads with one or moreelectrodes. Such a brain lead may be any lead capable of sensing brainactivity such as EEG. For example, brain monitoring element 18 may be adeep brain lead, a cortical lead or an electrode placed on the headexternally. Cardiac monitoring elements 14 may be cardiac leads or othertypes of sensors or electrodes capable of picking up cardiac signals.These monitoring elements allow detection of a neurological event andthe recording of data and signals pre and post event. Stored diagnosticdata is uplinked and evaluated by the patient's physician utilizingprogrammer 12 via a 2-way telemetry link 32. An external patientactivator 22 may optionally allow the patient 10, or other care provider(not shown), to manually activate the recording of diagnostic data. Animplant aid may be used with Monitor 200 to ensure a proper position andorientation during implant as described above in connection with thesystem of FIG. 1.

FIG. 6 is a simplified schematic view of a second embodiment of a fullMonitor 220 implanted in a patient 10. Monitor 220 continuously sensesand monitors cardiac, brain and respiration function of patient 10 viacardiac lead(s) 16 and a brain lead 18 to allow detection of aneurological event and the recording of data and signals pre and postevent. Stored diagnostic data is uplinked and evaluated by the patient'sphysician utilizing programmer 12 via a 2-way telemetry link 32. Anexternal patient activator 22 may optionally allow the patient 10, orother care provider (not shown), to manually activate the recording ofdiagnostic data.

FIG. 7 is a simplified schematic view of a third embodiment of a fullMonitor 240 implanted in a patient 10. Monitor 240 continuously sensesand monitors cardiac, brain and respiration function of patient 10 viasensor stub 20 and brain lead 18 to allow detection of a neurologicalevent and the recording of data and signals pre and post event. Storeddiagnostic data is uplinked and evaluated by the patient's physicianutilizing programmer 12 via a 2-way telemetry link 32. An externalpatient activator 22 may optionally allow the patient 10, or other careprovider (not shown), to manually activate the recording of diagnosticdata.

FIG. 8 is a simplified schematic view of a fourth embodiment of a fullMonitor 260 implanted in a patient 10. Monitor 260 in combination withexternal patch 160 continuously senses and monitors cardiac, brain andrespiration function of patient 10 to allow detection of a neurologicalevent and the recording of data and signals pre and post event. A 2-waywireless telemetry communication link 30 connects the Monitor unit 260and external patch 160. The wireless communication link 30 may consistof an RF link (such as described in U.S. Pat. No. 5,683,432 “AdaptivePerformance-Optimizing Communication System for Communicating with anImplantable Medical Device” to Goedeke, et al), an electromagnetic/ionictransmission (such as described in U.S. Pat. No. 4,987,897 “Body BusMedical Device Communication System” to Funke) or acoustic transmission(such as described in U.S. Pat. No. 5,113,859 “Acoustic Body Bus MedicalDevice Communication System” to Funke). Stored diagnostic data isuplinked and evaluated by the patient's physician utilizing programmer12 via a 2-way telemetry link 32. An external patient activator 22 mayoptionally allow the patient 10, or other care provider (not shown), tomanually activate the recording of diagnostic data. Also optionally, abutton 38 on the external patch monitor 160 may be activated by thepatient 10 to manually activate diagnostic data recording.

An alternative embodiment of the system of FIG. 8 consists of software“patches” or programs downloaded from a wearable patch 38 into animplanted neurostimulator, drug pump or monitor to allow researchevaluation of new therapies, detection algorithms, clinical research anddata gathering and the use of the patient as their own “control” byrandomly downloading or enabling a new detection algorithm or therapyand gathering the resultant clinical data (as substantially described inU.S. Pat. No. 6,200,265 “Peripheral Memory Patch and Access Method forUse with an Implantable Medical Device” to Walsh, et al). The clinicaland diagnostic data may be uploaded into the memory of the patch forlater retrieval and review by the patient's physician or device clinicalmanager. This embodiment also allows the upgrading of the existingimplant base with temporary new or additional therapeutic and diagnosticfeatures.

FIG. 9 is a simplified schematic view of a fifth embodiment of a fullMonitor 280 implanted in a patient 10. Monitor 280 continuously sensesand monitors cardiac, brain and respiration function of patient 10 viabrain lead 18 with integrated electrode 24 to allow detection of aneurological event and the recording of data and signals pre and postevent. Stored diagnostic data is uplinked and evaluated by the patient'sphysician utilizing programmer 12 via a 2-way telemetry link 32. Anexternal patient activator 22 may optionally allow the patient 10, orother care provider (not shown), to manually activate the recording ofdiagnostic data. Integrated electrode 24 senses ECG signals as describedabove in the referenced Klein '352 patent and respiration signals asdescribed above in the referenced Plicchi '892 and '251 patents.

FIG. 10 is a simplified schematic view of a sixth embodiment of a fullMonitor 26 implanted cranially in a patient 10. Monitor 26 continuouslysenses and monitors cardiac, brain and respiration function of patient10 to allow detection of a neurological event and the recording of dataand signals pre and post event. Stored diagnostic data is uplinked andevaluated by the patient's physician utilizing programmer 12 via a 2-waytelemetry link 32. An external patient activator 22 may optionally allowthe patient 10, or other care provider (not shown), to manually activatethe recording of diagnostic data.

Monitor 26 may be constructed as substantially described in USPublication No. 20040176817 “Modular implantable medical device” toWahlstrand et al. or U.S. Pat. No. 5,782,891 “Implantable CeramicEnclosure for Pacing, Neurological and Other Medical Applications in theHuman Body” to Hassler, et al or U.S. Pat. No. 6,427,086 “Means andMethod for the Intracranial Placement of a Neurostimulator” to Fischell.et al. EEG sensing is accomplished by the use of integrated electrodesin the housing of monitor 26 or, alternatively, by cranially implantedleads.

ECG sensing in the cranium may be accomplished by leadless ECG sensingas described in the above Brabec '940, Ceballos '915 and Lee '067referenced patents. Alternatively, ECG rate and asystole may be inferred(along with a blood pressure signal) from a capacitive dynamic pressuresignal (ie, dP/dt) as substantially described in U.S. Pat. No. 4,485,813“Implantable Dynamic Pressure Transducer System” to Anderson, et al. ECGrate and asystole may be inferred by monitoring an acoustic signal(i.e., sound) as substantially described in U.S. Pat. No. 5,554,177“Method and Apparatus to Optimize Pacing Based on Intensity of AcousticSignal” to Kieval, et al. The sensed acoustic signal is low passfiltered to limit ECG signals to 0.5-3 Hz while filtering out speech,swallowing and chewing sounds. ECG rate and asystole may be inferred(along with a blood saturation measurement) by monitoring a reflectanceoximetry signal (i.e., O₂sat) as substantially described in U.S. Pat.No. 4,903,701 “Oxygen Sensing Pacemaker” to Moore, et al. ECG rate andasystole may be inferred by monitoring a blood temperature signal (i.e.,dT/dt) as substantially described in U.S. Pat. No. 5,336,244“Temperature Sensor Based Capture Detection for a Pacer” to Weijand. ECGrate and asystole may be inferred (along with an arterial flowmeasurement) by monitoring a blood flow signal (from an adjacent veinvia impedance plethysmography, piezoelectric sensor or Dopplerultrasound) as substantially described in U.S. Pat. No. 5,409,009“Methods for Measurement of Arterial Blood Flow” to Olson. ECG rate andasystole may be inferred (along with a blood pressure measurement) bymonitoring a blood pressure signal utilizing a strain gaugesubstantially described in U.S. Pat. No. 5,168,759 “Strain Gauge forMedical Applications” to Bowman. ECG rate and asystole may be inferredby monitoring a blood parameter sensor (such as oxygen, pulse or flow)located on a V-shaped lead as substantially described in U.S. Pat. No.5,354,318 “Method and Apparatus for Monitoring Brain Hemodynamics” toTaepke.

Monitor 26 may warn or alert the patient 10 via an annunciator such asbuzzes, tones, beeps or spoken voice (as substantially described in U.S.Pat. No. 6,067,473 “Implantable Medical Device Using Audible SoundCommunication to Provide Warnings” to Greeninger, et al.) via apiezo-electric transducer incorporated in the housing of monitor 26 andtransmitting sound to the patient's 10 inner ear.

Monitor+Treatment (Brain)

FIG. 11 is a simplified schematic view of a full Monitor/Brain Therapyunit 300 implanted in a patient 10. Monitor/Brain Therapy unit 300continuously senses and monitors cardiac, brain and respiration functionof patient 10 via monitoring elements 14 and 18. Such monitoringelements may be subcutaneous electrodes and a brain lead to allowdetection of a neurological event, the recording of data and signals preand post event, and the delivery of therapy via brain lead. Storeddiagnostic data is uplinked and evaluated by the patient's physicianutilizing programmer 12 via a 2-way telemetry link 32. An externalpatient activator 22 may optionally allow the patient 10, or other careprovider (not shown), to manually activate the recording of diagnosticdata and delivery of therapy. An implant aid may be used withMonitor/Brain Therapy device 300 to assist with positioning andorientation during implant as described above in connection with thesystem of FIG. 1.

FIG. 12A is a simplified schematic view of a second embodiment of a fullMonitor/Brain Therapy unit 320 implanted in a patient 10. Monitor/BrainTherapy unit 320 continuously senses and monitors cardiac, brain andrespiration function of patient 10 via cardiac lead(s) 16 and a brainlead 18 to allow detection of a neurological event, the recording ofdata and signals pre and post event, and the delivery of therapy viabrain lead 18. Stored diagnostic data is uplinked and evaluated by thepatient's physician utilizing programmer 12 via a 2-way telemetry link32. An external patient activator 22 may optionally allow the patient10, or other care provider (not shown), to manually activate therecording of diagnostic data and delivery of therapy.

FIG. 12B is a simplified schematic view of a third embodiment of a fullMonitor/Brain Therapy system consisting of a thoracically implantedMonitor unit 321 in combination with a cranially implanted brainMonitor/Therapy unit 26. Monitor unit 321 continuously senses andmonitors the cardiac and respiration function of patient 10 via cardiaclead(s) 16 to allow detection of a neurological event, the recording ofdata and signals pre and post event, and the delivery of therapy viaMonitor/Therapy unit 26. A 2-way wireless telemetry communication link30 connects the Monitor/Therapy unit 26 and cardiac/respiration monitor321. The wireless communication link 30 may consist of an RF link (suchas described in U.S. Pat. No. 5,683,432 “Adaptive Performance-OptimizingCommunication System for Communicating with an Implantable MedicalDevice” to Goedeke, et al), an electromagnetic/ionic transmission (suchas described in U.S. Pat. No. 4,987,897 “Body Bus Medical DeviceCommunication System” to Funke) or acoustic transmission (such asdescribed in U.S. Pat. No. 5,113,859 “Acoustic Body Bus Medical DeviceCommunication System” to Funke). Monitor 26 may be constructed assubstantially described in US Publication No. 20040176817 “Modularimplantable medical device” to Wahlstrand et al. or U.S. Pat. No.5,782,891 “Implantable Ceramic Enclosure for Pacing, Neurological andOther Medical Applications in the Human Body” to Hassler, et al or U.S.Pat. No. 6,427,086 “Means and Method for the Intracranial Placement of aNeurostimulator” to Fischell. et al. EEG sensing and brain stimulationis accomplished by the use of integrated electrodes in the housing ofMonitor/Therapy unit 26 or, alternatively, by cranially implanted leads(not shown in FIG. 12B). Stored diagnostic data is uplinked andevaluated by the patient's physician utilizing programmer 12 via a 2-waytelemetry link 32. An external patient activator 22 may optionally allowthe patient 10, or other care provider (not shown), to manually activatethe recording of diagnostic data and delivery of therapy.

FIG. 13 is a simplified schematic view of a fourth embodiment of a fullMonitor/Brain Therapy unit 340 implanted in a patient 10. Monitor/BrainTherapy unit 340 continuously senses and monitors cardiac, brain andrespiration function of patient 10 via sensor stub 20 and a brain lead18 to allow detection of a neurological event such as a neurologicalevent, the recording of data and signals pre and post event, and thedelivery of therapy via brain lead 18. Stored diagnostic data isuplinked and evaluated by the patient's physician utilizing programmer12 via a 2-way telemetry link 32. An external patient activator 22 mayoptionally allow the patient 10, or other care provider (not shown), tomanually activate the recording of diagnostic data and delivery oftherapy.

FIG. 14 is a simplified schematic view of a fifth embodiment of a fullMonitor/Brain Therapy unit 360 implanted in a patient 10. Monitor/BrainTherapy unit 360 in combination with external patch 160 continuouslysenses and monitors cardiac, brain and respiration function of patient10 via external patch 160 and a brain lead 18 to allow detection ofneurological events, the recording of data and signals pre and postevent, and the delivery of therapy via brain lead 18. A 2-way wirelesstelemetry communication link 30 connects the Monitor/Brain Therapy unit360 and external patch 160. The wireless communication link 30 mayconsist of an RF link (such as described in U.S. Pat. No. 5,683,432“Adaptive Performance-Optimizing Communication System for Communicatingwith an Implantable Medical Device” to Goedeke, et al), anelectromagnetic/ionic transmission (such as described in U.S. Pat. No.4,987,897 “Body Bus Medical Device Communication System” to Funke) oracoustic transmission (such as described in U.S. Pat. No. 5,113,859“Acoustic Body Bus Medical Device Communication System” to Funke).Stored diagnostic data is uplinked and evaluated by the patient'sphysician utilizing programmer 12 via a 2-way telemetry link 32. Anexternal patient activator 22 may optionally allow the patient 10, orother care provider (not shown), to manually activate the recording ofdiagnostic data and delivery of therapy. Also optionally, a button 38 onthe external patch monitor 160 may be activated by the patient 10 tomanually activate diagnostic data recording and therapy delivery.

FIG. 15 is a simplified schematic view of a sixth embodiment of a fullMonitor/Brain Therapy unit 380 implanted in a patient 10. Monitor/BrainTherapy unit 380 continuously senses and monitors cardiac, brain andrespiration function of patient 10 via a brain lead 18 with integratedelectrode 24 to allow detection of neurological events, the recording ofdata and signals pre and post event, and the delivery of therapy viabrain lead 18. Stored diagnostic data is uplinked and evaluated by thepatient's physician utilizing programmer 12 via a 2-way telemetry link32. An external patient activator 22 may optionally allow the patient10, or other care provider (not shown), to manually activate therecording of diagnostic data and delivery of therapy. Integratedelectrode 24 senses ECG signals as described above in the referencedKlein '352 patent and respiration signals as described above in thereferenced Plicchi '892 and '251 patents.

FIG. 20 is a simplified schematic view of a seventh embodiment of a fullMonitor/Brain Therapy unit 26 implanted cranially in a patient 10.Monitor/Brain Therapy unit 26 in combination with leadless Monitor 400continuously senses and monitors cardiac, brain and respiration functionof patient 10 to allow detection of neurological events, the recordingof data and signals pre and post event, and the delivery of therapy viabrain lead 18. Stored diagnostic data is uplinked and evaluated by thepatient's physician utilizing programmer 12 via a 2-way telemetry link32. An external patient activator 22 may optionally allow the patient10, or other care provider (not shown), to manually activate therecording of diagnostic data and delivery of therapy. A 2-way wirelesstelemetry communication link 30 connects the Monitor/Therapy unit 26 andleadless Monitor 400. The wireless communication link 30 may consist ofan RF link (such as described in U.S. Pat. No. 5,683,432 “AdaptivePerformance-Optimizing Communication System for Communicating with anImplantable Medical Device” to Goedeke, et al), an electromagnetic/ionictransmission (such as described in U.S. Pat. No. 4,987,897 “Body BusMedical Device Communication System” to Funke) or acoustic transmission(such as described in U.S. Pat. No. 5,113,859 “Acoustic Body Bus MedicalDevice Communication System” to Funke). An implant aid may be used withMonitor device 400 to ensure a proper position and orientation duringimplant as described above in connection with the system of FIG. 1.Monitor 26 may be constructed as substantially described in USPublication No. 20040176817 “Modular implantable medical device” toWahlstrand et al. or U.S. Pat. No. 5,782,891 “Implantable CeramicEnclosure for Pacing, Neurological and Other Medical Applications in theHuman Body” to Hassler, et al or U.S. Pat. No. 6,427,086 “Means andMethod for the Intracranial Placement of a Neurostimulator” to Fischell.et al. EEG sensing is accomplished by the use of integrated electrodesin the housing of monitor 26 or, alternatively, by cranially implantedleads.

Monitor 26 may warn/alert the patient 10 via an annunciator such as, butnot limited to, buzzes, tones, beeps or spoken voice (as substantiallydescribed in U.S. Pat. No. 6,067,473 “Implantable Medical Device UsingAudible Sound Communication to Provide Warnings” to Greeninger, et al.)via a piezo-electric transducer incorporated in the housing of monitor26 and transmitting sound to the patient's 10 inner ear.

FIG. 21 is a simplified schematic view of an eighth embodiment of a fullMonitor/Brain Therapy unit 420 implanted cranially in a patient 10.Monitor/Brain Therapy unit 400 in combination with external patch coremonitor 160 continuously senses and monitors cardiac, brain andrespiration function of patient 10 to allow detection of neurologicalevents, the recording of data and signals pre and post event, and thedelivery of therapy via brain lead 18. Stored diagnostic data isuplinked and evaluated by the patient's physician utilizing programmer12 via a 2-way telemetry link 32. An external patient activator 22 mayoptionally allow the patient 10, or other care provider (not shown), tomanually activate the recording of diagnostic data and delivery oftherapy. A 2-way wireless telemetry communication link 30 connects theMonitor/Therapy unit 26 and leadless Monitor 400. The wirelesscommunication link 30 may consist of an RF link (such as described inU.S. Pat. No. 5,683,432 “Adaptive Performance-Optimizing CommunicationSystem for Communicating with an Implantable Medical Device” to Goedeke,et al), an electromagnetic/ionic transmission (such as described in U.S.Pat. No. 4,987,897 “Body Bus Medical Device Communication System” toFunke) or acoustic transmission (such as described in U.S. Pat. No.5,113,859 “Acoustic Body Bus Medical Device Communication System” toFunke).

Monitor 26 may be constructed as substantially described in USPublication No. 20040176817 “Modular implantable medical device” toWahlstrand et al. or U.S. Pat. No. 5,782,891 “Implantable CeramicEnclosure for Pacing, Neurological and Other Medical Applications in theHuman Body” to Hassler, et al or U.S. Pat. No. 6,427,086 “Means andMethod for the Intracranial Placement of a Neurostimulator” to Fischell.et al. EEG sensing is accomplished by the use of integrated electrodesin the housing of monitor 26 or, alternatively, by cranially implantedleads.

Monitor 26 may warn/alert the patient 10 via an annunciator such as, butnot limited to, buzzes, tones, beeps or spoken voice (as substantiallydescribed in U.S. Pat. No. 6,067,473 “Implantable Medical Device UsingAudible Sound Communication to Provide Warnings” to Greeninger, et al.)via a piezo-electric transducer incorporated in the housing of monitor26 and transmitting sound to the patient's 10 inner ear.

Monitor+Treatment (Brain+Respiration)

FIG. 16A is a simplified schematic view of a full Monitor/Brain andRespiration Therapy unit 440 implanted in a patient 10. Monitor/Brainand Respiration Therapy unit 440 continuously senses and monitorscardiac, brain and respiration function of patient 10 via cardiaclead(s) 16 and a brain lead 18 to allow detection of neurologicalevents, the recording of data and signals pre and post event, and thedelivery of therapy via brain lead 18 and phrenic nerve lead 28. Storeddiagnostic data is uplinked and evaluated by the patient's physicianutilizing programmer 12 via a 2-way telemetry link 32. An externalpatient activator 22 may optionally allow the patient 10, or other careprovider (not shown), to manually activate the recording of diagnosticdata and delivery of therapy. Optionally, lead 28 may connect to thediaphragm to provide direct diaphragmatic stimulation.

FIG. 16B is a simplified schematic view of a second embodiment of a fullMonitor/Brain and Respiration Therapy system consisting of athoracically implanted Monitor/Respiration Therapy unit 441 incombination with a cranially implanted brain Monitor/Therapy unit 26.Monitor unit 441 continuously senses and monitors the cardiac andrespiration function of patient 10 via cardiac lead(s) 16 to allowdetection of neurological events, the recording of data and signals preand post event, the delivery of respiration therapy via phrenic nervelead 28 and the delivery of brain stimulation via Monitor/Therapy unit26. A 2-way wireless telemetry communication link 30 connects theMonitor/Therapy unit 26 and cardiac/respiration monitor and respirationtherapy unit 441. The wireless communication link 30 may consist of anRF link (such as described in U.S. Pat. No. 5,683,432 “AdaptivePerformance-Optimizing Communication System for Communicating with anImplantable Medical Device” to Goedeke, et al), an electromagnetic/ionictransmission (such as described in U.S. Pat. No. 4,987,897 “Body BusMedical Device Communication System” to Funke) or acoustic transmission(such as described in U.S. Pat. No. 5,113,859 “Acoustic Body Bus MedicalDevice Communication System” to Funke). Monitor 26 may be constructed assubstantially described in US Publication No. 20040176817 “Modularimplantable medical device” to Wahlstrand et al. or U.S. Pat. No.5,782,891 “Implantable Ceramic Enclosure for Pacing, Neurological andOther Medical Applications in the Human Body” to Hassler, et al or U.S.Pat. No. 6,427,086 “Means and Method for the Intracranial Placement of aNeurostimulator” to Fischell. et al. EEG sensing and brain stimulationis accomplished by the use of integrated electrodes in the housing ofmonitor 26 or, alternatively, by cranially implanted leads (not shown inFIG. 16B). Stored diagnostic data is uplinked and evaluated by thepatient's physician utilizing programmer 12 via a 2-way telemetry link32. An external patient activator 22 may optionally allow the patient10, or other care provider (not shown), to manually activate therecording of diagnostic data and delivery of therapy. Optionally, lead28 may connect to the diaphragm to provide direct diaphragmaticstimulation.

FIG. 17 is a simplified schematic view of a third embodiment of a fullMonitor/Brain and Respiration Therapy unit 460 implanted in a patient10. Monitor/Brain and Respiration Therapy unit 460 continuously sensesand monitors cardiac, brain and respiration function of patient 10 viasensor stub 20 and a brain lead 18 to allow detection of neurologicalevents, the recording of data and signals pre and post event, and thedelivery of therapy via brain lead 18 and phrenic nerve lead 28. Storeddiagnostic data is uplinked and evaluated by the patient's physicianutilizing programmer 12 via a 2-way telemetry link 32. An externalpatient activator 22 may optionally allow the patient 10, or other careprovider (not shown), to manually activate the recording of diagnosticdata and delivery of therapy. Optionally, lead 28 may connect to thediaphragm to provide direct diaphragmatic stimulation.

FIG. 18 is a simplified schematic view of a fourth embodiment of a fullMonitor/Brain and Respiration Therapy unit 480 implanted in a patient10. Monitor/Brain and Respiration Therapy unit 480 continuously sensesand monitors cardiac, brain and respiration function of patient 10 via abrain lead 18 with integrated electrode 24 to allow detection ofneurological events, the recording of data and signals pre and postevent, and the delivery of therapy via brain lead 18 and phrenic nervelead 28. Stored diagnostic data is uplinked and evaluated by thepatient's physician utilizing programmer 12 via a 2-way telemetry link32. An external patient activator 22 may optionally allow the patient10, or other care provider (not shown), to manually activate therecording of diagnostic data and delivery of therapy. Optionally, lead28 may connect to the diaphragm to provide direct diaphragmaticstimulation. Integrated electrode 24 senses ECG signals as describedabove in the referenced Klein '352 patent and respiration signals asdescribed above in the referenced Plicchi '892 and '251 patents.

FIG. 19 is a simplified schematic view of a fifth embodiment of a fullMonitor/Brain and Respiration Therapy unit 500 implanted in a patient10. Monitor/Brain and Respiration Therapy unit 500 continuously sensesand monitors cardiac, brain and respiration function of patient 10 viabrain lead 18 and respiration lead 28 with integrated electrode 24 toallow detection of neurological events, the recording of data andsignals pre and post event, and the delivery of therapy via brain lead18 and phrenic nerve lead 28. Stored diagnostic data is uplinked andevaluated by the patient's physician utilizing programmer 12 via a 2-waytelemetry link 32. An external patient activator 22 may optionally allowthe patient 10, or other care provider (not shown), to manually activatethe recording of diagnostic data and delivery of therapy. Optionally,lead 28 may connect to the diaphragm to provide direct diaphragmaticstimulation. Integrated electrode 24 senses ECG signals as describedabove in the referenced Klein '352 patent and respiration signals asdescribed above in the referenced Plicchi '892 and '251 patents.

Monitor+Treatment (Brain+Cardiac)

FIG. 24A is a simplified schematic view of a full Monitor/Brain andCardiac Therapy unit 520 implanted in a patient 10. Monitor/Brain andCardiac Therapy unit 520 continuously senses and monitors cardiac, brainand respiration function of patient 10 via cardiac lead(s) 16 and abrain lead 18 to allow detection of neurological events, the recordingof data and signals pre and post event, and the delivery of therapy viabrain lead 18 and cardiac lead(s) 16. Stored diagnostic data is uplinkedand evaluated by the patient's physician utilizing programmer 12 via a2-way telemetry link 32. An external patient activator 22 may optionallyallow the patient 10, or other care provider (not shown), to manuallyactivate the recording of diagnostic data and delivery of therapy.

FIG. 24B is a simplified schematic view of a second embodiment of a fullMonitor/Brain and Cardiac Therapy system consisting of a thoracicallyimplanted Monitor/Therapy unit 521 implanted in patient 10 incombination with a cranially implanted brain Monitor/Therapy unit 26.Monitor/Therapy unit 521 continuously senses and monitors the cardiacand respiration function of patient 10 via cardiac lead(s) 16 to allowdetection of neurological events, the recording of data and signals preand post event, the delivery of cardiac therapy via Monitor/Therapy unit521 and the delivery of therapy via Monitor/Therapy unit 26. A 2-waywireless telemetry communication link 30 connects the Monitor/Therapyunit 26 and cardiac/respiration Monitor/Therapy unit 521. The wirelesscommunication link 30 may consist of an RF link (such as described inU.S. Pat. No. 5,683,432 “Adaptive Performance-Optimizing CommunicationSystem for Communicating with an Implantable Medical Device” to Goedeke,et al), an electromagnetic/ionic transmission (such as described in U.S.Pat. No. 4,987,897 “Body Bus Medical Device Communication System” toFunke) or acoustic transmission (such as described in U.S. Pat. No.5,113,859 “Acoustic Body Bus Medical Device Communication System” toFunke). Monitor 26 may be constructed as substantially described in USPublication No. 20040176817 “Modular implantable medical device” toWahlstrand et al. or U.S. Pat. No. 5,782,891 “Implantable CeramicEnclosure for Pacing, Neurological and Other Medical Applications in theHuman Body” to Hassler, et al or U.S. Pat. No. 6,427,086 “Means andMethod for the Intracranial Placement of a Neurostimulator” to Fischell.et al. EEG sensing and brain stimulation is accomplished by the use ofintegrated electrodes in the housing of monitor 26 or, alternatively, bycranially implanted leads (not shown in FIG. 24B). Stored diagnosticdata is uplinked and evaluated by the patient's physician utilizingprogrammer 12 via a 2-way telemetry link 32. An external patientactivator 22 may optionally allow the patient 10, or other care provider(not shown), to manually activate the recording of diagnostic data anddelivery of therapy.

FIG. 22 is a simplified schematic view of a third embodiment of a fullMonitor/Brain and Cardiac Therapy unit 540 implanted cranially in apatient 10. Monitor/Brain and Cardiac Therapy unit 540 in combinationwith external patient worn vest 34 continuously senses and monitorscardiac, brain and respiration function of patient 10 to allow detectionof neurological events, the recording of data and signals pre and postevent, and the delivery of therapy via brain lead 18 and vest 34. Storeddiagnostic data is uplinked and evaluated by the patient's physicianutilizing programmer 12 via a 2-way telemetry link 32. An externalpatient activator 22 may optionally allow the patient 10, or other careprovider (not shown), to manually activate the recording of diagnosticdata and delivery of therapy. A 2-way wireless telemetry communicationlink 30 connects the monitor/therapy unit 540 and patient worn vest 34.The wireless communication link 30 may consist of an RF link (such asdescribed in U.S. Pat. No. 5,683,432 “Adaptive Performance-OptimizingCommunication System for Communicating with an Implantable MedicalDevice” to Goedeke, et al), an electromagnetic/ionic transmission (suchas described in U.S. Pat. No. 4,987,897 “Body Bus Medical DeviceCommunication System” to Funke) or acoustic transmission (such asdescribed in U.S. Pat. No. 5,113,859 “Acoustic Body Bus Medical DeviceCommunication System” to Funke).

Monitor/Therapy unit 540 may be constructed as substantially describedin US Publication No. 20040176817 “Modular implantable medical device”to Wahlstrand et al. or U.S. Pat. No. 5,782,891 “Implantable CeramicEnclosure for Pacing, Neurological and Other Medical Applications in theHuman Body” to Hassler, et al or U.S. Pat. No. 6,427,086 “Means andMethod for the Intracranial Placement of a Neurostimulator” to Fischell.et al. EEG sensing is accomplished by the use of integrated electrodesin the housing of Monitor/Therapy unit 540 or, alternatively, bycranially implanted leads.

Monitor/Therapy unit 540 may warn/alert the patient 10 via anannunciator such as, but not limited to, buzzes, tones, beeps or spokenvoice (as substantially described in U.S. Pat. No. 6,067,473“Implantable Medical Device Using Audible Sound Communication to ProvideWarnings” to Greeninger, et al.) via a piezo-electric transducerincorporated in the housing of monitor 26 and transmitting sound to thepatient's 10 inner ear.

FIG. 23 is a simplified schematic view of a fourth embodiment of a fullMonitor/Brain and Cardiac Therapy unit 560 implanted cranially in apatient 10. Monitor/Brain and Cardiac Therapy unit 560 in combinationwith leadless defibrillator 36 continuously senses and monitors cardiac,brain and respiration function of patient 10 to allow detection ofneurological events, the recording of data and signals pre and postevent, and the delivery of therapy via brain lead 18 and defibrillator36. Stored diagnostic data is uplinked and evaluated by the patient'sphysician utilizing programmer 12 via a 2-way telemetry link 32. Anexternal patient activator 22 may optionally allow the patient 10, orother care provider (not shown), to manually activate the recording ofdiagnostic data and delivery of therapy. A 2-way wireless telemetrycommunication link 30 connects the monitor/therapy unit 560 and leadlessdefibrillator 36. The wireless communication link 30 may consist of anRF link (such as described in U.S. Pat. No. 5,683,432 “AdaptivePerformance-Optimizing Communication System for Communicating with anImplantable Medical Device” to Goedeke, et al), an electromagnetic/ionictransmission (such as described in U.S. Pat. No. 4,987,897 “Body BusMedical Device Communication System” to Funke) or acoustic transmission(such as described in U.S. Pat. No. 5,113,859 “Acoustic Body Bus MedicalDevice Communication System” to Funke).

Monitor/Therapy unit 560 may be constructed as substantially describedin US Publication No. 20040176817 “Modular implantable medical device”to Wahlstrand et al. or U.S. Pat. No. 5,782,891 “Implantable CeramicEnclosure for Pacing, Neurological and Other Medical Applications in theHuman Body” to Hassler, et al or U.S. Pat. No. 6,427,086 “Means andMethod for the Intracranial Placement of a Neurostimulator” to Fischell.et al. EEG sensing is accomplished by the use of integrated electrodesin the housing of Monitor/Therapy unit 560 or, alternatively, bycranially implanted leads.

Monitor/Therapy unit 560 may warn/alert the patient 10 via anannunciator such as, but not limited to, buzzes, tones, beeps or spokenvoice (as substantially described in U.S. Pat. No. 6,067,473“Implantable Medical Device Using Audible Sound Communication to ProvideWarnings” to Greeninger, et al.) via a piezo-electric transducerincorporated in the housing of Monitor/Therapy unit 560 and transmittingsound to the patient's 10 inner ear.

Monitor+Treatment (Brain+Respiration+Cardiac)

FIG. 25A is a simplified schematic view of a full Monitor/Brain,Respiration and Cardiac Therapy unit 580 implanted in a patient 10.Monitor/Brain, Respiration and Cardiac Therapy unit 580 continuouslysenses and monitors cardiac, brain and respiration function of patient10 via cardiac lead(s) 16 and a brain lead 18 to allow detection ofneurological events, the recording of data and signals pre and postevent, and the delivery of therapy via brain lead 18, cardiac lead(s) 16and phrenic nerve lead 28. Stored diagnostic data is uplinked andevaluated by the patient's physician utilizing programmer 12 via a 2-waytelemetry link 32. An external patient activator 22 may optionally allowthe patient 10, or other care provider (not shown), to manually activatethe recording of diagnostic data and delivery of therapy. Optionally,lead 28 may connect to the diaphragm to provide direct diaphragmaticstimulation.

FIG. 25B is a simplified schematic view of a second embodiment of a fullMonitor/Brain, Respiration and Cardiac Therapy system consisting of athoracically implanted Monitor/Respiration Therapy unit 581 incombination with a cranially implanted brain Monitor/Therapy unit 26.Monitor/Therapy unit 581 continuously senses and monitors the cardiacand respiration function of patient 10 via cardiac lead(s) 16 to allowdetection of neurological events, the recording of data and signals preand post event, the delivery of respiration therapy via phrenic nervelead 28 and the delivery of brain stimulation via Monitor/Therapy unit26. A 2-way wireless telemetry communication link 30 connects theMonitor/Therapy unit 26 and cardiac/respiration monitor/therapy unit581. The wireless communication link 30 may consist of an RF link (suchas described in U.S. Pat. No. 5,683,432 “Adaptive Performance-OptimizingCommunication System for Communicating with an Implantable MedicalDevice” to Goedeke, et al), an electromagnetic/ionic transmission (suchas described in U.S. Pat. No. 4,987,897 “Body Bus Medical DeviceCommunication System” to Funke) or acoustic transmission (such asdescribed in U.S. Pat. No. 5,113,859 “Acoustic Body Bus Medical DeviceCommunication System” to Funke). Monitor 26 may be constructed assubstantially described in US Publication No. 20040176817 “Modularimplantable medical device” to Wahlstrand et al. or U.S. Pat. No.5,782,891 “Implantable Ceramic Enclosure for Pacing, Neurological andOther Medical Applications in the Human Body” to Hassler, et al or U.S.Pat. No. 6,427,086 “Means and Method for the Intracranial Placement of aNeurostimulator” to Fischell. et al. EEG sensing and brain stimulationis accomplished by the use of integrated electrodes in the housing ofmonitor 26 or, alternatively, by cranially implanted leads (not shown inFIG. 25B). Stored diagnostic data is uplinked and evaluated by thepatient's physician utilizing programmer 12 via a 2-way telemetry link32. An external patient activator 22 may optionally allow the patient10, or other care provider (not shown), to manually activate therecording of diagnostic data and delivery of therapy. Optionally, lead28 may connect to the diaphragm to provide direct diaphragmaticstimulation.

Core Monitor Design

Turning now to FIG. 26, there is shown a block diagram of the electroniccircuitry that makes up core Monitor 100 (FIG. 1) in accordance with oneembodiment of the invention. As can be seen from FIG. 26, Monitor 100comprises a primary control circuit 720. Much of the circuitryassociated with primary control circuit 720 is of conventional design,in accordance, for example, with what is disclosed in U.S. Pat. No.5,052,388 to Sivula et al, entitled “Method and Apparatus forImplementing Activity Sensing in a Pulse Generator.” To the extent thatcertain components of Monitor 100 are purely conventional in theirdesign and operation, such components will not be described herein indetail, as it is believed that design and implementation of suchcomponents would be a matter of routine to those of ordinary skill inthe art. For example, primary control circuit 720 in FIG. 26 includessense amplifier circuitry 724, a crystal clock 728, a random-accessmemory and read-only memory (RAM/ROM) unit 730, a central processingunit (CPU) 732, a MV Processor circuit 738 and a telemetry circuit 734,all of which are well-known in the art.

Monitor 100 preferably includes internal telemetry circuit 734 so thatit is capable of being programmed by means of externalprogrammer/control unit 12 via a 2-way telemetry link 32 (shown in FIG.1). Programmers and telemetry systems suitable for use in the practiceof the present invention have been well known for many years. Knownprogrammers typically communicate with an implanted device via abi-directional radio-frequency telemetry link, so that the programmercan transmit control commands and operational parameter values to bereceived by the implanted device, and so that the implanted device cancommunicate diagnostic and operational data to the programmer.Programmers believed to be suitable for the purposes of practicing thepresent invention include the Models 9790 and CareLink® programmers,commercially available from Medtronic, Inc., Minneapolis, Minn. Varioustelemetry systems for providing the necessary communications channelsbetween an external programming unit and an implanted device have beendeveloped and are well known in the art. Telemetry systems believed tobe suitable for the purposes of practicing the present invention aredisclosed, for example, in the following U.S. patents: U.S. Pat. No.5,127,404 to Wyborny et al. entitled “Telemetry Format for ImplantedMedical Device”; U.S. Pat. No. 4,374,382 to Markowitz entitled “MarkerChannel Telemetry System for a Medical Device”; and U.S. Pat. No.4,556,063 to Thompson et al. entitled “Telemetry System for a MedicalDevice”.

Typically, telemetry systems such as those described in the abovereferenced patents are employed in conjunction with an externalprogramming/processing unit. Most commonly, telemetry systems forimplantable medical devices employ a radio-frequency (RF) transmitterand receiver in the device, and a corresponding RF transmitter andreceiver in the external programming unit. Within the implantabledevice, the transmitter and receiver utilize a wire coil as an antennafor receiving downlink telemetry signals and for radiating RF signalsfor uplink telemetry. The system is modeled as an air-core coupledtransformer. An example of such a telemetry system is shown in theabove-referenced Thompson et al. '063 patent.

In order to communicate digital data using RF telemetry, a digitalencoding scheme such as is described in the above-reference Wyborny etal. '404 patent can be used. In particular, for downlink telemetry apulse interval modulation scheme may be employed, wherein the externalprogrammer transmits a series of short RF “bursts” or pulses in whichthe interval between successive pulses (e.g., the interval from thetrailing edge of one pulse to the trailing edge of the next) ismodulated according to the data to be transmitted. For example, ashorter interval may encode a digital “0” bit while a longer intervalencodes a digital “1” bit.

For uplink telemetry, a pulse position modulation scheme may be employedto encode uplink telemetry data. For pulse position modulation, aplurality of time slots are defined in a data frame, and the presence orabsence of pulses transmitted during each time slot encodes the data.For example, a sixteen-position data frame may be defined, wherein apulse in one of the time slots represents a unique four-bit portion ofdata.

As depicted in FIG. 26, programming units such as the above-referencedMedtronic Models 9790 and CareLink® programmers typically interface withthe implanted device through the use of a programming head orprogramming paddle, a handheld unit adapted to be placed on thepatient's body over the implant site of the patient's implanted device.A magnet in the programming head effects reed switch closure in theimplanted device to initiate a telemetry session. Thereafter, uplink anddownlink communication takes place between the implanted device'stransmitter and receiver and a receiver and transmitter disposed withinthe programming head.

As previously noted, primary control circuit 720 includes centralprocessing unit 732 which may be an off-the-shelf programmablemicroprocessor or microcontroller, but in the presently preferredembodiment of the invention is a custom integrated circuit. Althoughspecific connections between CPU 732 and other components of primarycontrol circuit 720 are not shown in FIG. 26, it will be apparent tothose of ordinary skill in the art that CPU 732 functions to control thetimed operation of sense amplifier circuit 724 under control ofprogramming stored in RAM/ROM unit 730. It is believed that those ofordinary skill in the art will be familiar with such an operativearrangement.

With continued reference to FIG. 26, crystal oscillator circuit 728, inthe presently preferred embodiment a 32,768-Hz crystal controlledoscillator, provides main timing clock signals to primary controlcircuit 720.

It is to be understood that the various components of monitor 100depicted in FIG. 26 are powered by means of a battery (not shown), whichis contained within the hermetic enclosure of monitor 100, in accordancewith common practice in the art. For the sake of clarity in the figures,the battery and the connections between it and the other components ofmonitor 100 are not shown.

With continued reference to FIG. 26, sense amplifier 724 is coupled tomonitoring elements 14 such as subcutaneous electrodes. Cardiacintrinsic signals are sensed by sense amplifier 724 as substantiallydescribed in U.S. Pat. No. 6,505,067 “System and Method for Deriving aVirtual ECG or EGM Signal” to Lee, et al. Further processing by CPU 732allows the detection of cardiac electrical characteristics/anomalies(e.g., heart rate, heart rate variability, arrhythmias, cardiac arrest,sinus arrest and sinus tachycardia) that would be a matter of routine tothose of ordinary skill in the art.

Further processing of the cardiac signal amplitudes may be used todetect respiration characteristics/anomalies (e.g., respiration rate,tidal volume, minute ventilation, and apnea) in MV Processor 738. FIG.27 shows the intracardiac signals 770 presented to sense amplifier 724from monitoring elements 14. Note the amplitude variation of cardiacsignals caused by the change in thoracic cavity pressure due torespiration (ie, inspiration and expiration). By low pass filtering thecardiac signals 770, a signal representing minute ventilation may beobtained as depicted in waveform 772 (FIG. 27). This respiration signalmay further be examined to detect respiration rate and reduced orabsence of inspiration and expiration (central apnea) by CPU 732 andsoftware resident in RAM/ROM 730.

Upon detection of either a cardiac or respiration anomaly, CPU 732,under control of computer executable instruction in firmware resident inRAM/ROM 730, will initiate recording of the appropriate diagnosticinformation into RAM of RAM/ROM 730, initiate a warning or alert to thepatient, patient caregiver, or remote monitoring location. See flowdiagram and description as described below in association with FIG. 31.

Turning now to FIG. 28, there is shown a block diagram of the electroniccircuitry that makes up core Monitor 120 (FIG. 2) in accordance withanother disclosed embodiment of the invention. As can be seen from FIG.28, Monitor 120 comprises a primary control circuit 720 and a minuteventilation circuit 722. Much of the circuitry associated with primarycontrol circuit 720 is of conventional design, in accordance, forexample, with what is disclosed in U.S. Pat. No. 5,052,388 to Sivula etal, entitled “Method and Apparatus for Implementing Activity Sensing ina Pulse Generator.” To the extent that certain components of Monitor 120are purely conventional in their design and operation, such componentswill not be described herein in detail, as it is believed that designand implementation of such components would be a matter of routine tothose of ordinary skill in the art. For example, primary control circuit720 in FIG. 28 includes sense amplifier circuitry 724, a crystal clock728, a random-access memory and read-only memory (RAM/ROM) unit 730, acentral processing unit (CPU) 732, and a telemetry circuit 734, all ofwhich are well-known in the art.

Monitor 120 preferably includes internal telemetry circuit 734 so thatit is capable of being programmed by means of externalprogrammer/control unit 12 via a 2-way telemetry link 32 (shown in FIG.2). Programmers and telemetry systems suitable for use in the practiceof the present invention have been well known for many years. Knownprogrammers typically communicate with an implanted device via abidirectional radio-frequency telemetry link, so that the programmer cantransmit control commands and operational parameter values to bereceived by the implanted device, and so that the implanted device cancommunicate diagnostic and operational data to the programmer.Programmers believed to be suitable for the purposes of practicing thepresent invention include the Models 9790 and CareLink® programmers,commercially available from Medtronic, Inc., Minneapolis, Minn. Varioustelemetry systems for providing the necessary communications channelsbetween an external programming unit and an implanted device have beendeveloped and are well known in the art. Telemetry systems believed tobe suitable for the purposes of practicing the present invention aredisclosed, for example, in the following U.S. patents: U.S. Pat. No.5,127,404 to Wyborny et al. entitled “Telemetry Format for ImplantedMedical Device”; U.S. Pat. No. 4,374,382 to Markowitz entitled “MarkerChannel Telemetry System for a Medical Device”; and U.S. Pat. No.4,556,063 to Thompson et al. entitled “Telemetry System for a MedicalDevice”.

Typically, telemetry systems such as those described in the abovereferenced patents are employed in conjunction with an externalprogramming/processing unit. Most commonly, telemetry systems forimplantable medical devices employ a radio-frequency (RF) transmitterand receiver in the device, and a corresponding RF transmitter andreceiver in the external programming unit. Within the implantabledevice, the transmitter and receiver utilize a wire coil as an antennafor receiving downlink telemetry signals and for radiating RF signalsfor uplink telemetry. The system is modeled as an air-core coupledtransformer. An example of such a telemetry system is shown in theabove-referenced Thompson et al. '063 patent.

In order to communicate digital data using RF telemetry, a digitalencoding scheme such as is described in the above-reference Wyborny etal. '404 patent can be used. In particular, for downlink telemetry apulse interval modulation scheme may be employed, wherein the externalprogrammer transmits a series of short RF “bursts” or pulses in whichthe interval between successive pulses (e.g., the interval from thetrailing edge of one pulse to the trailing edge of the next) ismodulated according to the data to be transmitted. For example, ashorter interval may encode a digital “0” bit while a longer intervalencodes a digital “1” bit.

For uplink telemetry, a pulse position modulation scheme may be employedto encode uplink telemetry data. For pulse position modulation, aplurality of time slots are defined in a data frame, and the presence orabsence of pulses transmitted during each time slot encodes the data.For example, a sixteen-position data frame may be defined, wherein apulse in one of the time slots represents a unique four-bit portion ofdata.

As depicted in FIG. 28, programming units such as the above-referencedMedtronic Models 9790 and CareLink® programmers typically interface withthe implanted device through the use of a programming head orprogramming paddle, a handheld unit adapted to be placed on thepatient's body over the implant site of the patient's implanted device.A magnet in the programming head effects reed switch closure in theimplanted device to initiate a telemetry session. Thereafter, uplink anddownlink communication takes place between the implanted device'stransmitter and receiver and a receiver and transmitter disposed withinthe programming head.

With continued reference to FIG. 28, Monitor 120 is coupled to leads 16which, when implanted, extend transvenously between the implant site ofMonitor 120 and the patient's heart (not shown). For the sake ofclarity, the connections between leads 16 and the various components ofMonitor 120 are not shown in FIG. 28, although it will be clear to thoseof ordinary skill in the art that, for example, leads 16 willnecessarily be coupled, either directly or indirectly, to senseamplifier circuitry 724 in accordance with common practice, such thatcardiac electrical signals may be conveyed to sensing circuitry 724, vialeads 16. Cardiac leads 16 may consist of any typical lead configurationas is known in the art, such as, without limitation, right ventricular(RV) pacing or defibrillation leads, right atrial (RA) pacing ordefibrillation leads, single pass RA/RV pacing or defibrillation leads,coronary sinus (CS) pacing or defibrillation leads, left ventricularpacing or defibrillation leads, pacing or defibrillation epicardialleads, subcutaneous defibrillation leads, unipolar or bipolar leadconfigurations, or any combinations of the above lead systems.

Sensed cardiac events are evaluated by CPU 732 and software stored inRAM/ROM unit 730. Cardiac anomalies detected include heart ratevariability, QT variability, QT_(C), sinus arrest, syncope, ST segmentelevation and various arrhythmias such as sinus, atrial and ventriculartachycardias.

Heart rate variability may be measured by the method and apparatus asdescribed in U.S. Pat. No. 5,749,900 “Implantable Medical DeviceResponsive to Heart Rate Variability Analysis” to Schroeppel, et al andU.S. Pat. No. 6,035,233 “Implantable Medical Device Responsive to HeartRate Variability Analysis” to Schroeppel, et al. Schroeppel '900 and'233 patents describe an implantable cardiac device that computes timeintervals occurring between successive heartbeats and then derive ameasurement of heart rate variability from epoch data for predeterminedtime periods. The Schroeppel device then compares measurement of heartrate variability with previously stored heart rate variability zones,which define normal and abnormal heart rate variability.

QT variability may be measured by the method and apparatus as describedin U.S. Pat. No. 5,560,368 “Methodology for Automated QT VariabilityMeasurement” to Berger. The Berger '368 patent utilizes a “stretchable”QT interval template started at the beginning of the QRS complex andterminating on the T-wave to determine beat-to-beat variability.

QT_(C) may be measured by the method and apparatus as described in U.S.Pat. No. 6,721,599 “Pacemaker with Sudden Rate Drop Detection Based onQT Variations” to de Vries. The de Vries '599 patent measures QTinterval real time and compares the instantaneous value to a calculatedmean via a preprogrammed threshold change value.

Syncope may be detected by the methods and apparatus as described inU.S. Pat. No. 6,721,599 “Pacemaker with Sudden Rate Drop Detection Basedon QT Variations” to de Vries. The de Vries '599 patent utilizes asudden rate change and a real time QT interval measurement compared to aQT mean to detect sudden rate drop and neurally mediated syncope.

ST segment elevation (an indicator of myocardial ischemia) may bedetected by the methods and apparatus as described in U.S. Pat. No.6,128,526 “Method for Ischemia Detection and Apparatus for Using Same”to Stadler, et al and U.S. Pat. No. 6,115,630 “Determination ofOrientation of Electrocardiogram Signal in Implantable Medical devices”to Stadler, et al. The Stadler '526 and '630 patents describe a systemthat compares a sampled data point prior to an R-wave complex peakamplitude to multiple samples post R-wave event to detect ST segmentelevation.

Arrhythmias such as sinus, atrial and ventricular tachycardias may bedetected by the methods and apparatus as described in U.S. Pat. No.5,545,186 “Prioritized Rule Based Method and Apparatus for Diagnosis andTreatment of Arrhythmias” to Olson, et al.

Sinus arrest may be detected by the methods and apparatus as describedabove in the Olson '186 patent.

In the presently disclosed embodiment, two leads are employed—an atriallead 16A having atrial TIP and RING electrodes, and a ventricular lead16V having ventricular TIP and RING electrodes. In addition, as notedabove, the conductive hermetic canister of Monitor 120 serves as anindifferent electrode.

As previously noted, primary control circuit 720 includes centralprocessing unit 732 which may be an off-the-shelf programmablemicroprocessor or microcontroller, but in the presently preferredembodiment of the invention is a custom integrated circuit. Althoughspecific connections between CPU 732 and other components of primarycontrol circuit 720 are not shown in FIG. 28, it will be apparent tothose of ordinary skill in the art that CPU 732 functions to control thetimed operation of sense amplifier circuit 724 under control ofprogramming stored in RAM/ROM unit 730. It is believed that those ofordinary skill in the art will be familiar with such an operativearrangement.

With continued reference to FIG. 28, crystal oscillator circuit 728, inthe presently preferred embodiment a 32,768-Hz crystal controlledoscillator, provides main timing clock signals to primary controlcircuit 720 and to minute ventilation circuit 722.

It is to be understood that the various components of Monitor 120depicted in FIG. 28 are powered by means of a battery (not shown), whichis contained within the hermetic enclosure of Monitor 120, in accordancewith common practice in the art. For the sake of clarity in the figures,the battery and the connections between it and the other components ofMonitor 120 are not shown.

As shown in FIG. 28, primary control circuit 720 is coupled to minuteventilation circuit 722 by means of multiple signal lines, designatedcollectively as 738 in FIG. 28. An I/O interface 740 in primary controlcircuit 720 and a corresponding I/O interface 742 in minute ventilationcircuit 722, coordinate the transmission of signals between the twounits via control lines 738.

Minute ventilation circuit 722 measures changes in transthoracicimpedance, which has been shown to be proportional to minuteventilation. Minute ventilation is the product of tidal volume andrespiration rate, and as such is a physiologic indicator of changes inmetabolic demand.

Monitor 120, in accordance with the presently disclosed embodiment ofthe invention, measures transthoracic impedance using a bipolar lead 16and a tripolar measurement system. As will be hereinafter described ingreater detail, minute ventilation circuit 722 delivers 30-microSecbiphasic current excitation pulses of 1-mA (peak-to-peak) between a RINGelectrode of bipolar lead 16 and the conductive canister of monitor 120,functioning as an indifferent electrode CASE, at a rate of 16-Hz. Theresulting voltage is then measured between a TIP electrode of lead 16and the monitor 120 CASE electrode. Such impedance measurement may beprogrammed to take place in either the atrium or ventricle of thepatient's heart.

The impedance signal derived by minute ventilation circuit 722 has threemain components: a DC offset voltage; a cardiac component resulting fromthe heart's function; and a respiratory component. The frequencies ofthe cardiac and respiratory components are assumed to be identical totheir physiologic origin. Since the respiratory component of theimpedance signal derived by minute ventilation circuit 722 is of primaryinterest for this aspect of the present invention, the impedance signalis subjected to filtering in minute ventilation low-pass filter (MV LPF)750 having a passband of 0.05- to 0.8-Hz (corresponding to 3-48 breathsper minute) to remove the DC and cardiac components.

With continuing reference to FIG. 28, minute ventilation circuit 722includes a Lead Interface circuit 744 which is essentially a multiplexerthat functions to selectively couple and decouple minute ventilationcircuit 722 to the VTIP, VRING, ATIP, ARING, and CASE electrodes, aswill be hereinafter described in greater detail.

Coupled to lead interface circuit 744 is a minute ventilation (MV)Excitation circuit 746 which functions to deliver the biphasicconstant-current pulses between various combinations of lead electrodes(VTIP, VRING, etc.) for the purpose of measuring cardiac impedance. Inparticular, MV Excitation circuit 746 delivers biphasic excitationpulses (at a rate of 16-Hz between the ventricular ring electrode VRINGand the pacemaker canister CASE) of the type delivered in accordancewith the method and apparatus described in U.S. Pat. No. 5,271,395“Method and Apparatus for Rate Responsive Cardiac Pacing” to Wahlstrandet al.

To measure cardiac impedance, minute ventilation circuit 722 monitorsthe voltage differential present between pairs of electrodes asexcitation pulses are being injected as described above. Again, theelectrodes from which voltage differentials are monitored will varydepending upon whether atrial or ventricular measurements are beingmade. In one embodiment of the invention, the same electrodes (i.e.,VRING and CASE for ventricular, ARING and CASE for atrial) are used forboth delivery of excitation pulses and voltage differential monitoring.It is contemplated, however, that the electrode combinations forexcitation and measurement may be among the programmable settings, whichmay be altered post-implant with the programming system.

With continued reference to FIG. 28, the 16-Hz sampled output voltagesfrom ZMEAS PREAMP circuit 748 are presented to the minute ventilationlow-pass filter circuit MV LPF 750, which has a passband of 0.05-0.8 Hzin the presently preferred embodiment of the invention. Again, it isbelieved that the design and implementation of MV LPF circuit 750 wouldbe a matter of routine engineering to those of ordinary skill in theart. The output from MV LPF circuit 750 is a voltage waveform whoselevel at any given time is directly proportional to cardiac impedancemeasured between the selected electrodes. Thus, the MV LPF output signalwill be referred to herein as an impedance waveform. MV Calculation 752analyzes the impedance waveform to determine/detect respiration rate,tidal volume, minute ventilation and presence of apnea.

The circuit of FIG. 28 may additionally monitor pulmonary edema bymeasuring the DC impedance between the distal electrodes of cardiacleads 16 and the case of core monitor 120. Measurement technique may beas substantially described in U.S. Pat. No. 6,512,949 “ImplantableMedical Device for Measuring Time Varying Physiologic ConditionsEspecially Edema and for Responding Thereto” by Combs, et al.

Upon detection of a cardiac or respiration anomaly, CPU 732, undercontrol of firmware resident in RAM/ROM 730, will initiate recording ofthe appropriate diagnostic information into RAM of RAM/ROM 730, initiatea warning or alert to the patient, patient caregiver, or remotemonitoring location. See flow diagram and description as described belowin association with FIG. 31.

Turning now to FIG. 29, there is shown a block diagram of the electroniccircuitry that makes up core Monitor 140 with sensor stub 20 (FIG. 3) inaccordance with another disclosed embodiment of the invention. As can beseen from FIG. 29, Monitor 140 comprises a primary control circuit 720and a minute ventilation circuit 722, the function of which has beendescribed in detail above in conjunction with the system of FIG. 28.Monitor 140 measures thoracic impedance from the case of monitor 140 tothe distal end of a sensor stub lead 20 (a subcutaneously implantedsensor lead) via an impedance/voltage converter using a samplingfrequency of approximately 16 Hz as substantially described in U.S. Pat.No. 4,596,251 “Minute Ventilation Dependant Rate Responsive Pacer” toPlicchi, et al. Respiration parameters are evaluated by CPU 732 andsoftware resident in RAM/ROM 730.

Cardiac signals are sensed by sense amplifier 724 and evaluated by CPU732 and software resident in RAM/ROM 730.

Upon detection of either/or a cardiac or respiration anomaly, CPU 732,under control of firmware resident in RAM/ROM 730, will initiaterecording of the appropriate diagnostic information into RAM of RAM/ROM730, initiate a warning or alert to the patient, patient caregiver, orremote monitoring location. See flow diagram and description asdescribed below in association with FIG. 31.

Turning now to FIG. 30, there is shown a block diagram of the electroniccircuitry that makes up external patch core Monitor 160 (FIG. 4) inaccordance with another disclosed embodiment of the invention. As can beseen from FIG. 30, Monitor 160 comprises a primary control circuit 720and a minute ventilation circuit 722, the function of which has beendescribed in detail above in conjunction with the system of FIG. 28.Intrinsic cardiac signals are sensed by electrodes 161 affixed to thepatient's skin, amplified by amplifier 724 and processed by CPU 732 andsoftware program resident in RAM/ROM 730. Cardiac anomalies are detectedsuch as heart rate variability, QT variability, QT_(C), sinus arrest,and various arrhythmias such as sinus, atrial and ventriculartachycardias. Respiration sensing is accomplished by low pass filteringthe sensed and amplified intrinsic cardiac signals as shown in FIG. 27.Respiration anomalies (such as reduced or cessation of tidal volume andapnea) are evaluated and detected by CPU 732 and software resident inRAM/ROM 730.

Upon detection of either/or a cardiac or respiration anomaly, CPU 732,under control of firmware resident in RAM/ROM 730, will initiaterecording of the appropriate diagnostic information into RAM of RAM/ROM730, initiate a warning or alert to the patient, patient caregiver, orremote monitoring location. See flow diagram and description asdescribed below in association with FIG. 31.

FIG. 31 is a flow diagram 800 showing operation of a core Monitorsensing/monitoring cardiac and respiration parameters for the detectionof neurological events as shown and described in embodiments in FIG. 1-4above. Beginning at block 802, the interval between sensed cardiacsignals are measured. At block 804, a rate stability measurement is madeon each cardiac interval utilizing a heart rate average from block 806.At block 808, a rate stable decision is made based upon preprogrammedparameters. If YES, the flow diagram returns to the HR Measurement block802. If NO, the rate stability information is provided to FormatDiagnostic Data block 812.

At block 816, thoracic impedance is continuously measured in a samplingoperation. At block 818, a MV and respiration rate calculation is made.At block 822, a pulmonary apnea decision is made based uponpreprogrammed criteria. If NO, the flow diagram returns to MVMeasurement block 816. If YES, the occurrence of apnea and MVinformation is provided to Format Diagnostic Data block 812. FormatDiagnostic Data block 812 formats the data from the cardiac andrespiration monitoring channels, adds a time stamp (ie, date and time)and provides the data to block 814 where the data is stored in RAM, SRAMor MRAM memory for later retrieval by a clinician via telemetry.Optionally, block 812 may add examples of intrinsic ECG or respirationsignals recorded during a sensed episode/seizure. Additionally,optionally, block 815 may initiate a warning or alert to the patient,patient caregiver, or remote monitoring location (as described in U.S.Pat. No. 5,752,976 “World Wide Patient Location and Data TelemetrySystem for Implantable Medical Devices” to Duffin, et al.

Full Monitor Design

FIG. 32 is a block diagram of the electronic circuitry that makes upfull Monitor 200 (FIG. 5) in accordance with the presently disclosedalternative embodiment of the invention. As can be seen from FIG. 32,Monitor 200 includes a primary control circuit 720 that is describedherein above in conjunction with FIG. 26. In addition the full monitorof FIG. 30 also includes an amplifier 725 to amplify and sense EEGsignals from a cranially implanted lead 18. The CPU 732, in conjunctionwith a software program resident in RAM/ROM 730, evaluates theinformation from the sensed cardiac, respiration and EEG signals,detects the onset of cerebral, cardiac or respiratory anomalies, mayperform one or more algorithms or methods as described in thisspecification (such as determination of concordance between EEG andcardiac or respiratory signals, comparison of heart rates associatedwith certain neurological event time periods, etc.), formats and storesdiagnostic data for later retrieval by the patient's clinician and,optionally, may warn or alert the patient, patient caregiver or remotemonitoring location. See flow diagram and description below inassociation with FIG. 37.

FIG. 33 is a block diagram of the electronic circuitry that makes upfull Monitor 220 with brain 18 and cardiac 16 leads (FIG. 6) inaccordance with the presently disclosed alternative embodiment of theinvention. As can be seen from FIG. 33, Monitor 220 comprises a primarycontrol circuit 720 and MV circuit 722 that are described herein abovein conjunction with FIG. 28. In addition, the full Monitor 220 of FIG.33 also includes an amplifier 725 to amplify and sense EEG signals froma cranially implanted lead 18. The CPU 732, in conjunction with asoftware program resident in RAM/ROM 730, integrates the informationfrom the sensed cardiac, respiration and EEG signals, detects the onsetof cerebral, cardiac or respiratory anomalies, formats and storesdiagnostic data for later retrieval by the patient's clinician and,optionally, may warn or alert the patient, patient caregiver or remotemonitoring location. See flow diagram and description as described belowin association with FIG. 37.

FIG. 34 is a block diagram of the electronic circuitry that makes upfull Monitor 240 with a brain lead 18 and sensor stub 20 (FIG. 7) inaccordance with the presently disclosed alternative embodiment of theinvention. As can be seen from FIG. 34, Monitor 240 comprises a primarycontrol circuit 720 and MV circuit 722 that are described herein abovein conjunction with FIG. 28. In addition, the full Monitor 240 of FIG.34 also includes an amplifier 725 to amplify and sense EEG signals froma cranially implanted lead 18. The CPU 732, in conjunction with asoftware program resident in RAM/ROM 730, integrates the informationfrom the sensed cardiac, respiration and EEG signals, detects the onsetof cerebral, cardiac or respiratory anomalies, formats and storesdiagnostic data for later retrieval by the patient's clinician and,optionally, may warn or alert the patient, patient caregiver or remotemonitoring location. See flow diagram and description as described belowin association with FIG. 37.

FIG. 35 is a block diagram of the electronic circuitry that makes upexternal patch 160/full Monitor 260 with a brain lead 18 (FIG. 8) inaccordance with the presently disclosed alternative embodiment of theinvention. As can be seen from FIG. 35, Monitor 260 comprises a primarycontrol circuit 720 and external patch comprises a cardiac/MV (minuteventilation) circuit 160, the functions of which have been described indetail above in conjunction with the system of FIG. 28. Intrinsiccardiac signals are sensed by electrodes affixed to the patient's skin,amplified by amplifier 724, sent to primary control circuit 720 andprocessed by CPU 732 and software program resident in RAM/ROM 730.Cardiac anomalies are detected such as heart rate variability, QTvariability, QT_(C), sinus arrest, and various arrhythmias such assinus, atrial and ventricular tachycardias. Respiration sensing isaccomplished by low pass filtering the sensed and amplified intrinsiccardiac signals as shown in FIG. 27 or, alternatively, by using the MV/Zmeasurement circuitry of external patch 160 as described above inconnection with FIG. 28. Respiration anomalies (such as reduced orcessation of tidal volume and apnea) are evaluated and detected by CPU732 and software resident in RAM/ROM 730.

The CPU 732, in conjunction with a software program resident in RAM/ROM730, integrates the information from the sensed cardiac, respiration andEEG signals, detects the onset of cerebral, cardiac or respiratoryanomalies, formats and stores diagnostic data for later retrieval by thepatient's clinician and, optionally, may warn or alert the patient,patient caregiver or remote monitoring location. See flow diagram anddescription as described below in association with FIG. 37.

The circuitry and function of the device 240 shown in FIG. 34 anddescribed herein above may also be used for the full Monitor 280 withintegrated electrode 24 brain lead 18 (FIG. 9). As described above inassociation with core Monitor 240, thoracic impedance viaimpedance/voltage converter as measured from the case of monitor 240 tothe sensor stub 20 using a sampling frequency of approximately 16 Hz assubstantially described in U.S. Pat. No. 4,596,251 “Minute VentilationDependant Rate Responsive Pacer” to Plicchi, et al. The Monitor 280 ofthis alternative embodiment utilizes the same circuitry of Monitor 240but connected to the integrated electrode 24 on brain lead 18 instead ofthe sensor stub of Monitor 240.

Upon detection of either/or a cardiac or respiration anomaly, CPU 732,under control of firmware resident in RAM/ROM 730, will initiaterecording of the appropriate diagnostic information into RAM of RAM/ROM730, initiate a warning or alert to the patient, patient caregiver, orremote monitoring location. See flow diagram and description asdescribed below in association with FIG. 37.

FIG. 36 is a block diagram of the electronic circuitry that makes upfull Monitor 26 (FIG. 10) in accordance with the presently disclosedalternative embodiment of the invention. As can be seen from FIG. 32,Monitor 26 comprises a primary control circuit 720 whose function isdescribed herein above in conjunction with FIG. 26. In addition the fullMonitor 26 of FIG. 32 also includes an EEG amplifier 725 to amplify andsense EEG signals from a cranially implanted lead 18 or, alternatively,device mounted electrodes. Additionally, Sensor Interface 727 powers up,amplifies and senses the cardiac and respiratory signals from anyone ormore of the following cranially implanted sensors. ECG sensing in thecranium may be accomplished by leadless ECG sensing as described in theabove Brabec '940, Ceballos '915 and Lee '067 referenced patents.Alternatively, cardiac rate and asystole may be inferred from a dP/dtsignal described above in the Anderson '813 patent; an acoustic signaldescribed above in the Kieval '177 patent; an O₂sat signal describedabove in Moore '701 patent; a dT/dt signal described above in theWeijand '244 patent; a flow signal described above in the Olson '009; astrain gauge signal described above in the Bowman '759 patent; and ablood parameter sensor (such as oxygen, pulse or flow) located on aV-shaped lead described in the Taepke '318 patent.

The CPU 732, in conjunction with a software program resident in RAM/ROM730, integrates the information from the sensed cardiac, respiration andEEG signals, detects the onset of cerebral, cardiac or respiratoryanomalies, formats and stores diagnostic data for later retrieval by thepatient's clinician and, optionally, may warn or alert the patient,patient caregiver or remote monitoring location. See flow diagram anddescription as described below in association with FIG. 37.

FIG. 37 is a flow diagram 840 showing operation of a full monitorsensing and monitoring cardiac, respiration and electroencephalogramparameters for the detection of neurological events as shown anddescribed in embodiments in FIG. 5-10 above. Beginning at block 802, theinterval between sensed cardiac signals are measured. At block 804, arate stability measurement is made on each cardiac interval utilizing aheart rate average from block 806. At block 808, a rate stable decisionis made based upon preprogrammed parameters. If YES, the flow diagramreturns to the HR Measurement block 802. If NO, the rate stabilityinformation is provided to Format Diagnostic Data block 812.

At block 816, thoracic impedance is continuously measured in a samplingoperation. At block 818, a MV and respiration rate calculation is made.At block 822, a pulmonary apnea decision is made based uponpreprogrammed criteria. If NO, the flow diagram returns to MVMeasurement block 816. If YES, the occurrence of apnea and MVinformation is provided to Format Diagnostic Data block 812.

At block 824, the electroencephalogram is sensed and measured. An EEGseizure determination is performed at block 826 as described in USpublished application 2004/0138536 “Clustering of Recorded PatientNeurological Activity to Determine Length of a Neurological Event” toFrei, et al incorporated herein by reference. At block 828, a seizurecluster episode is determined. If NO, the flow diagram returns to EEGMeasurement block 824. If YES, the occurrence of a seizure cluster isprovided to Format Diagnostic Data block 812. Format Diagnostic Datablock 812 formats the data from the cardiac, respiration and EEGmonitoring channels, adds a time stamp (ie, date and time) and providesthe data to block 814 where the data is stored in RAM memory for laterretrieval by a clinician via telemetry. Optionally, block 812 may addexamples of intrinsic ECG, respiration or EEG signals recorded during asensed episode/seizure. Additionally, optionally, block 815 may initiatea warning or alert to the patient, patient caregiver, or remotemonitoring location (as described in U.S. Pat. No. 5,752,976 “World WidePatient Location and Data Telemetry System for Implantable MedicalDevices” to Duffin, et al.

FIG. 38 is a diagram 850 of exemplary physiologic data from a patient 10with a full monitor as described herein above showing an EEG signal 852and an ECG signal 854. A first epileptic seizure is shown at 856(pre-ictal segment 851, ictal segment 853 and post-ictal segment 855)and detected at 864 and a second seizure is shown at 858 (pre-ictalsegment 857, ictal segment 859 and post-ictal segment 861) and detectedat 866 by the full monitor. The ECG signal 854 shows a first arrhythmicepisode at 860 and detected at 868 and a second arrhythmic episode at862 and detected at 870 by the full monitor. Note that the firstepileptic seizure 864 and arrhythmic episode 868 are co-incident and“matched”. Note that in the diagram 850 arrhythmic episode 870 andseizure episode 866 are not co-incident and are “unmatched”.

Segmenting a Cardiac or Respiratory Signal According to Brain DetectionResults

One embodiment of the inventive system provides an automated method ofprocessing cardiac signals in a full monitoring device for a nervoussystem disorder, to screen for cardiac abnormalities/heart rate changesand respiratory abnormalities during or within a specified time periodof a neurological event. This embodiment medical device system andmethod reports a patient's heart or pulmonary condition for eachneurological event detected in the brain signal.

In a monitoring device for epilepsy, brain signals aremonitored/processed with a seizure detection algorithm; the cardiac andrespiratory signals are passively recorded during the brain signalprocessing. When a seizure has been detected in the brain signal datastream, a recording containing a montage of brain, cardiac andrespiratory signals is created. The signals in the recording are thenpost-processed to evaluate the patient's heart and pulmonary condition.A description of the post-processed design is shown in FIG. 39.

FIG. 39 shows a process 750 for identifying ECG and respiratoryabnormalities recorded during detected seizures. At block 751, the fullmonitor monitors EEG and ECG or respiratory signals. At block 752, themonitor detects seizures in EEG signals. At block 753, seizure detectiontriggers recording of EEG, ECG and respiratory signals. After uplinkingto a programmer, the ECG/respiratory signals are post processed. Atblock 755, ECG and respiratory signals are segmented into (a) pre-ictal,(b) ictal, and (c) post-ictal periods, as defined in the correspondingEEG for the detected seizure. The ictal periods are automaticallyderived from a seizure-detection algorithm operating on the EEG signals.For example, the beginning of the ictal period may be time-marked todetection cluster onset; the end of the ictal period by detectioncluster offset (as described in published US Application No.2004/0138536 “Clustering of Recorded Patient Neurological Activity toDetermine Length of a Neurological Event” to Frei, et al incorporatedherein by reference in its entirety). The durations of the pre-ictal andpost-ictal periods are programmable. It may be desirable to program thepre-ictal period for purposes of a cardiac baseline or respiratorybaseline as ending some period of time before the true ictal period asdetermined by the EEG detector. In this way a better baseline may beobtained that is not distorted by changes in cardiac or respiratoryactivity near in time to the neurological event.

At block 756, the loop-recorded data is screened for abnormalities.After the ECG and respiratory signals are segmented, the differentintervals of ECG and respiratory data are separately processed to detectevents reflected in those signals. For example, detection of a cardiacevent may include computation of indices of heart rate (HR) (i.e., mean,median, max, std. dev., etc.) or indications of an some abnormal heartactivity such as an arrhythmia which are displayed in the physicianprogrammer for each detected event. A respiratory event may bedetermined from many signals including, but not limited to, minuteventilation, respiration rate, apnea, or edema, which are displayed inthe physician programmer for each detected event. To monitor changes incardiovascular and pulmonary function that may arise from or causeseizures, percentage of change between indices is calculated. Forexample, to indicate magnitude of change in heart rate from a baselineto seizure state, the percentage of change between the pre-ictal(baseline) and ictal (seizure) periods is computed/displayed.% Chg. Detect Onset=(Ictal HR indices−Base HR indices)/Base HR indices

Comparison between the post-ictal and baseline periods is also performedto evaluate if and when a return to baseline is achieved.% Chg. Detect End=(Post-Ictal HR indices−Base HR indices)/Base HRindices

During processing, the time at which the post-ictal heart rate returnsto baseline, relative to the end of the ictal period, is identified. Thephysician may choose to increase the duration of the post-ictal periodif, during detected seizures, the patient's HR indices do notconsistently return to baseline levels.

At block 757, detection times for arrhythmic and respiratory anomaliesare determined. The ECG and respiratory signals are further processed,via an arrhythmia/abnormality detection algorithm, to identify ECG andrespiratory abnormalities (bradycardia, tachycardia, asystole, STsegment depression, QT_(C) prolongation, apnea, edema, etc.). Suchevents may occur in different periods of data, and cross ictalboundaries (e.g., a tachy event may begin prior to seizure onset, andcontinue well after seizure termination, resulting in a detection thatincludes all intervals of data). Thus, during screening the entire ECGand respiration signals in the loop recording data is processed in asingle step, without segmentation. The start and end times for eachidentified arrhythmia/abnormality in the loop recording data is storedand later retrieved for analysis.

The physician runs a matching test (EEG detections versus ECG orrespiratory detections) at block 758. The matching test is run tocompare the EEG detections and ECG/respiratory detections in the looprecording data. The matching test reports whether each ECG/respiratoryabnormality is coincident with (i.e., matched), or is temporallyseparated from, the detected seizure (i.e., unmatched). In the case of amatch, the time difference between EEG detection onset andECG/respiratory detection onset is computed.

At block 759, the matching test results are evaluated to determine ifthe seizure is associated with an arrhythmia or respiratory anomaly. Atblock 760, additional seizures are determined. If NO, block 761 reportsresults of ECG/respiratory screening procedures for each seizure. Atblock 760, if the result is YES the flow diagram returns to block 752.

ECG/respiratory post-processing may occur in the implantable device,after the loop recorded data has been stored to memory. Alternatively,the post-processing may occur on loop-recorded data transmitted to anexternal wearable device or physician programmer or other computer.

Determination of Improvements in Neurological Event Detection UsingCardiac or Respiratory Input

Another embodiment of the invention is a medical device system andmethod for determining whether cardiopulmonary signals may be used toimprove neurological event detection. This medical device systemincludes a brain monitoring element (e.g., lead 18, external electrode),a cardiac monitoring element (e.g., lead 16, sensor stub 20, sensor 14,integrated electrode 24, external electrode, etc.) or respiratorymonitoring element (e.g., lead 16, sensor stub 20, sensor 14, integratedelectrode 24, external electrode, etc.) and a processor (e.g., CPU 732or any other processor or combination of processors implanted orexternal). This determination of whether cardiac or respiratory signalsmay be used to improve neurological event detection may be verybeneficial to understanding a patient's condition and that in turn ishelpful to determining appropriate treatment or prevention options. Themedical device system may include the ability to determine relationshipsbetween brain and heart only, brain and respiratory only, or both. Oncethese relationships are better understood, they may be utilized to makedecisions about enabling the use of cardiac signals or cardiacdetections or respiratory signals or respiratory detections in themonitoring or treatment of the neurological disorder. Note that thismedical device system and method may be performed by many differenttypes of hardware embodiments including the example hardware embodimentsprovided in this specification as well as in an external computer orprogrammer. The executable instructions executed by a processor may bestored in any computer readable medium such as, for example only, RAM730.

The determination of improvements in neurological event detection usingcardiopulmonary input includes determination of concordance betweenbrain and cardiac signals or between brain and respiratory signals,determination of detection latency, and the false positive rate in thecardiac or respiratory signal relative to a neurological event detectedin the brain signal.

An example of the usefulness of this determination is provided here. Ifit is determined that a patient with epilepsy has improvement inneurological event detection based on a cardiac signal it may bedesirable to enable the use of a cardiac activity detection algorithm totrigger application of therapy to the brain. Another example of thebenefit of concordance information is that a high concordance betweenbrain and heart (including perhaps concordance with a particular type ofcardiac event) for an individual with epilepsy, may mean that thepatient is more susceptible to SUDEP. Perhaps steps can be taken such asuse or implantation of a heart assist device such as a pacemaker ordefibrillator for this patient to reduce the likelihood of death. Thereare of course many other examples of situations that may be discoveredby operation of this concordance system and method that result in betterhealth care.

The medical device system with concordance capability may include abrain monitoring element 18 (e.g., EEG lead with one or more electrodes)for sensing activity of the brain and outputting a brain signal, and acardiac or respiratory monitoring element 14 (e.g., electrodes or othersensors) or both, for sensing a cardiac or respiratory activity andoutputting a cardiac or respiratory signal, and a processor. Theprocessor is configured to receive the brain signal and one or more ofthe cardiac and respiratory signals and to compare the brain signal andone of the cardiac or respiratory signals to each other.

Comparison of the brain and cardiac signals to each other may take manydifferent forms. In one embodiment, the processor is configured toobtain information identifying one or more neurological events in thebrain signal, and to also obtain information identifying one or morecardiac events in the cardiac signal. “Obtain” means 1) automaticallygenerating the information by executing an algorithm that evaluates thesignal, or 2) receiving the information from a user such as a physicianreviewing the brain and cardiac signals (this second aspect of obtain ishereinafter referred to as “manual identification of events”). Thealgorithm or physician may create or generate various features of theneurological event such as a determination of when the event begins andends and hence a duration of the event. For example automatic generationof the information may be performed by a seizure detection algorithmsuch as described in US published application 2004/0138536 “Clusteringof Recorded Patient Neurological Activity to Determine Length of aNeurological Event” to Frei, et al. Likewise in the case of a cardiacsignal, any algorithm that evaluates a cardiac signal and outputsinformation about cardiac activity or abnormalities would be anautomatic generation of the information. Some examples are presentedabove in the discussion of the core monitor. An example of a manualidentification of an event includes a physician indicating to aphysician programmer the temporal location of a neurological event andalso indicating the temporal location of cardiac or respiratory events.This temporal location of an event may include marking of the beginningand end of the event.

In the case of manual identification of an event, the medical devicesystem may include a user interface (for example, on a programmer orcomputer), for display of the brain, cardiac and respiration signals.The user, such as a physician, may mark events on the programmer. Forexample, the physician could mark the location by clicking a cursor overthe location on the monitor. In another example, the physician couldmark a location with a stylus on a touch sensitive screen. The physicianmarkings may include marks that indicate the beginning and the end of anevent.

In a more specific embodiment, the comparison of the brain signal to thecardiac or respiration signal includes for each neurological event,determining whether the neurological event is within a specified timeperiod of one of the one or more cardiac or respiratory events, and foreach of the one or more cardiac or respiratory events determiningwhether the cardiac or respiratory event is within a specified timeperiod of one of the one or more neurological events. Two events are“within a specified time period” of each other if the two events areoverlapping in time or the amount of time between two reference pointsof the two events is less than a time period that is previouslydetermined and set in the device or that has been programmed or may beprogrammed into the device. Reference points of an event are somemeasure or indication of the temporal position of the event. Forexample, the two reference points may be the end of the first of theevents to end and the beginning of the other event. Other referencepoints may be used such as, but not limited to, the midpoints of each ofthe events. An example of a specified time period that could beprogrammed into the device is 10 seconds. So in this example, theneurological event and the cardiac event would be within the specifiedtime period of each other if a chosen reference point for the cardiacevent (e.g., end of the cardiac event) was within 10 seconds of a chosenreference point (e.g., beginning of the neurological event) for theneurological event.

The comparison of brain signal to cardiac signal may include thefollowing: determining the number of neurological events that arematched with a cardiac event (i.e., within a specified time period of acardiac event); determining the number of neurological events that arematched with a cardiac event (i.e., not within the specified time periodof a cardiac event); and determining the number of cardiac events thatare not within the specified time period of a neurological event (thefalse positive rate in the ECG signal). The same steps may be applied inthe case of comparison of a brain signal to a respiratory signal.

Furthermore for matched events (events that are within the specifiedtime period of each other), the processor may determine the temporalrelationship of the neurological event and the matched cardiac event orbetween the neurological event and the matched respiratory event.Because matched events may overlap or they may not overlap, the temporalrelationship may be defined or described in many different ways. Oneembodiment of determining the temporal relationship is determining thetemporal order (which event is first to occur) of the matched events. Inorder to determine the temporal order between two events, a referencepoint must be determined. As mentioned earlier the reference point maybe the end, start or midpoint of an event, or the reference point may becomputed in some other way. In general a reference point indicates sometemporal information about the event. The reference points may then becompared to determine which occurred first. The event associated withthe first to occur reference point is then the first to occur event.

In another embodiment of comparing the brain signal to a cardiac orrespiratory signal, the processor is configured to compute a rate ofconcordance between the neurological events and the cardiac orrespiratory events. In this embodiment, the processor is configured tocategorize the neurological event as cardiac matched when there is acardiac event within a specified time period of the neurological event.The processor computes the rate of concordance between the neurologicalevents and the cardiac events based on the number of cardiac matchedevents and the number of neurological events. For example, the processormay compute the rate of concordance by calculating the number of cardiacmatched events divided by the number of neurological events. The morematches the greater the concordance.

In another embodiment the processor is further configured to perform thefollowing: dividing the neurological event into at least two segments;and assigning the cardiac event to one or more of the segments accordingto when the cardiac event occurred relative to the segments. Forexample, if the neurological event is a seizure, then there may be threesegments: a pre-ictal segment, an ictal segment, and a post ictalsegment. Various methods may be used to assign a cardiac event to one ofthese segments. For example, an algorithm executed by the processor(e.g., any of the processors of the many hardware embodiments in thisapplication such as cpu 732, or a processor in a programmer or othercomputer external to the body) may determine when the cardiac eventstarted relative to the three segments and assign the cardiac event tothe segment in which it started. Of course other methods, more complexor simple may be used to make this assignment.

The ECG algorithm may be automatically enabled/disabled for use inmonitoring or treatment (as described herein below) if concordance,detection latency and false positive rates meet selected andprogrammable criteria, indicating an improvement in neurological eventdetection performance. Alternatively, the patient's clinician may chooseto review matching results and manually enable/disable the ECG detectorbased on information provided. For example, detection of a cardiac eventmay result in turning a neurostimulator or drug delivery device on toprevent the onset of a seizure. Alternatively, detection of a cardiacevent may result in modification of therapy parameters. In anotheralternative, the ECG detector may be enabled for purposes of recordingECG, EEG or some other data.

In the embodiment that includes therapeutic output, the medical devicesystem further includes a neurological therapy delivery moduleconfigured to provide a therapeutic output to treat a neurologicaldisorder when the cardiac event detection algorithm detects a cardiacevent. A neurological therapy delivery module may be any module capableof delivery a therapy to the patient to treat a neurological disorder.For example, but not limited to, a neurological therapy delivery modulemay be an electrical stimulator (e.g., stimulator 729), drug deliverydevice, therapeutic patch, brain cooling module.

Depending on the individual patient, and depending on the particularneurological disorder of concern, there may be different levels ofconcordance between different types of cardiac events and theneurological events. Therefore, in another embodiment, the processor isfurther configured to obtain information categorizing each cardiac eventas one or more of two or more types of cardiac events. Types of cardiacevents are known by different signals or aspects of signals coming fromthe heart. Examples of different types of cardiac events include:tachyrhythmia, ST segment elevation, bradycardia, asystole. In thisembodiment, the processor may then determine concordance between eachtype of cardiac event or subset of cardiac events and neurologicalevents. One embodiment of such determination is a processor configuredto categorize each neurological event as first type cardiac matched whenthere is a first type cardiac event within a specified time period ofthe neurological event. The processor further categorizes theneurological event as second type cardiac matched when there is a secondtype cardiac event within a specified time period of the neurologicalevent. The processor further computes a first rate of concordancebetween the neurological events and the first type cardiac events basedon the number of first type cardiac matched events and the number ofneurological events. The processor also computes a second rate ofconcordance between the neurological events and the second type cardiacevents based on the number of second type cardiac matched events and thenumber of neurological events. This computation of rate of concordancemay be performed as many times as there are types of cardiac events. Thecategorization of events as well as the various computed rates ofconcordance may be stored in memory.

In the embodiment allowing for computation of specific type of cardiacevent rates of concordance, the medical device system may furtherinclude the capability to enable the use of detection of a particulartype of cardiac event to affect the provision of therapy to the patientfor the neurological disorder. For example, if it is determined that ahigh rate of concordance exists between tachyarrhythmia and seizure, theenablement of cardiac detection for affecting seizure therapy may belimited to the detection of tachyarrythmia. In this case the seizuretherapy will not be affected by other types of cardiac events.

It is noted that the medical device system may be external to thepatient's body, implanted or some combination. The processor itself maybe either external or implanted. For example, the processor may be in ahandheld unit such as a programmer, or the processor could be in ageneral purpose computer.

The various processor operations described above may be embodied inexecutable instructions and stored in a computer readable medium. Theprocessor then operates to perform the various steps via execution ofthese instructions. At one level, the executable instructions cause theprocessor to receive a brain signal from a brain monitoring element,receive a cardiac signal from a hear monitoring element, and compare thebrain signal to the cardiac signal.

As described above, in a full monitor device for epilepsy, EEG,respiratory and cardiac (ECG) physiologic signals are simultaneouslymonitored and processed by different algorithms. A seizure-detectionalgorithm detects seizure activity in the EEG signals. A secondalgorithm detects heart-rate changes, ECG abnormalities, or uniquewaveform patterns in the ECG signals, which may or may not be coincidentwith seizures. Additionally, a third algorithm detects minuteventilation, respiration rate and apnea, which also may or may not becoincident with seizures.

By default, the EEG is considered a ‘primary signal’—detections fromthis signal are used to represent seizure. The ECG and respiratorysignals are ‘secondary signals’—it is not initially known whether eventsdetected in these two signals are useful for seizure detection. In atreatment setting, the patient's clinician considers the stored signalsand data to determine if processing the ECG and respiratory signalsprovides added benefit in improving detection performance.

To make this determination, the patient is monitored until a sufficientnumber of detections in one or both of the data streams are observed(number of required events is programmable). Events detected in the EEGdata stream may be classified by the user, via the programmer interface,to indicate whether they are clinical seizures (TP-C), sub-clinicalseizures (TP-N), or false positive detections (FP). Likewise, eventsdetected in the ECG and respiratory signals may be classified toindicate type of abnormality detected.

The concordance between the EEG seizure detections and ECG andrespiratory signals is then evaluated. This is accomplished in one oftwo ways:

The relation between the EEG and ECG detections is initially unknown.Determination of the relationship between EEG and ECG may be performedwith post processing or in real time.

In the post processing embodiment, automated matching tests areperformed to identify the temporal relationship of detections in thedifferent data streams. The matching tests identify the number of EEGdetections that are within a specified time period with ECG orrespiratory abnormalities (EEG-ECG Match or EEG-Respiratory Match, see864 and 868 FIG. 38), and those that are not (EEG detect-ECG Normal orEEG detect-Respiratory Normal). For matched detections, the timedifference between EEG detection onset and ECG or respiratory detectiononset is computed (detection latency). The number of detected events inthe ECG or respiratory signals, independent of EEG triggered events, arealso computed (ECG Un-matched or Respiratory Un-Matched, see 870 FIG.38).

With the real time implementation, the device controls a flag set by theseizure-detection algorithm operating on EEG signals. The flag is areal-time indicator of the subject's seizure state (1=in EEG detectionstate; 0=out of EEG detection state). In real-time, the device monitorsthe co-occurrence of the EEG and ECG/respiratory detection states.

The following conditions are assessed:

Brain-Cardiac Match—The EEG event (e.g., seizure) is classified asmatched with ECG event if the ECG detection state occurs during an EEGdetection state or within a specified time period of an EEG detectionstate.

Brain-Respiratory Match—The EEG event (e.g., seizure) is classified asmatched with respiratory event if the respiratory detection state occursduring an EEG detection state or within a specified time period of anEEG detection state.

Brain Detect-Cardiac Normal—The EEG event (e.g., seizure) is classifiedas matched with normal ECG if no ECG detection state occurs during anEEG detection state or within a specified time period of an EEGdetection state.

Brain Detect-Respiratory Normal—The EEG event (e.g., seizure) isclassified as matched with normal respiration if no respiratorydetection state occurs during an EEG detection state or within aspecified time period of the EEG detection state.

Cardiac Un-Matched—An ECG event is classified as un-matched to EEG event(e.g., seizure) if no EEG detection state occurs during the ECGdetection state or within a specified time period of an ECG detectionstate.

Respiratory Un-Matched—A respiratory event is classified as un-matchedto EEG event (e.g., seizure) if no EEG detection state occurs during therespiratory detection state or within a specified time period of therespiratory detection state.

After EEG-ECG or EEG-respiratory matching has been performed, thephysician programmer indicates whether the following conditions aretrue: (1) a high rate of concordance between detections in the EEG andECG data streams (or between the EEG and respiratory data streams); (2)earlier detection in the ECG signal (or respiratory signal) relative toneurological event onset as indicated in the EEG signal; and (3) a lowrate of FP's in the ECG signal (or in the respiratory signal). If theseconditions are all true, this may indicate that the ECG signal (orrespiratory signal) provides value in neurological event detection(e.g., seizure detection).

Using this information, the physician may choose to activate the ECGalgorithm or activate the respiration algorithm—that is, enable it as aprimary signal for use in neurological event detection. Determination ofwhether to “add in” the ECG or respiratory signals (activate it incombination with the EEG signal) for seizure monitoring or treatment isbased on satisfying one or more of the above stated conditions. Thisprocess can be automated by defining programmable threshold values foreach of the stated conditions.

Note that ECG detection and respiratory detection may both be enabled oractivated for neurological event detection if they both meet theconditions above.

The physician may decide not to enable the ECG/respiratory algorithms ifthe matching tests show no additional improvements in detectionperformance using the ECG or respiratory signals, or if specificity inthe ECG/respiratory signals is low. In such cases, the physician mayenable a mode of passive ECG recording, with the intended use ofdocumenting cardiovascular changes during ictal periods in the EEG.

FIG. 40A shows a process 971 for determining whether to enable thecardiac or respiratory detection algorithms for neurological eventdetection. At block 974 the medical device system monitors a brainsignal and, cardiac or respiratory signals. At block 975 detections inany of the 3 signals (brain, cardiac, respiratory) triggers looprecording. Determination of the bounds of the neurological, cardiac andrespiratory events may be performed in various ways. In one embodimentthis determination of the bounds of events may be performed by aphysician. In another embodiment, such determination of the bounds ofthe events may be performed by detection algorithms executed by aprocessor. Block 991 represents this choice between physician markedevents and algorithm marked events. In the physician marking embodiment,the loop recording stored data must be uplinked to an external devicesuch as a programmer or other computer. Upon uplinking the looprecording stored data, the physician may score the onset, offset orother reference points in the brain signal at block 976. The physicianmay also classify the events as related or not to the particularneurological event being targeted. A matching test (brain detectionsversus cardiac or respiratory detections) is executed at block 977. Thebrain inputs to the matching test may be either physician markings(e.g., onset, offset of neurological event) or the automated scores fromthe neurological event detection algorithm. The matching test resultsfrom block 977 result in a summary of comparisons made between the brainand cardiac detections (or between the brain and respiratorydetections). At block 978 the matching test results are evaluated. Theevaluation at block 978 includes blocks 979, 980 and 981 (i.e., blocks979, 980 and 981 are components of block 978. At block 979 concordancebetween brain and cardiac/respiratory detections is determined. At block980 a cardiac or respiratory false positive rate (relative to theneurological signal) is evaluated using the cardiac un-matched events orthe respiratory un-matched events in the cardiac or respiratory signals.At block 981 cardiac/respiratory latency is evaluated for the matcheddetections. At block 982, neurological event detection improvement usingcardiac or respiration signals is considered based upon the abovedeterminations. If use of cardiac signals or respiratory signals doesnot improve neurological event detection (“NO” condition), then thephysician or other user may maintain or disable the cardiac eventdetection algorithm monitoring at block 983. If at block 982 the resultis YES, the cardiac or respiratory signal is activated for neurologicalevent monitoring or treatment.

Process 871 in FIG. 40B is one specific embodiment of process 971 inFIG. 40A. Process 871 is a process for determining whether to enable theECG or respiratory detection algorithms for seizure detection. At block874 the full monitor monitors EEG and ECG or respiratory signals. Atblock 875 detections in any of the 3 signals (EEG, ECG or respiratory)triggers loop recording. Determination of the bounds of the seizure, ECGand respiratory events may be performed in various ways. In oneembodiment this determination of the bounds of a seizure may beperformed by a physician. In another embodiment, such determination ofthe bounds of the events may be performed by detection algorithmsexecuted by a processor. Block 891 represents this choice betweenphysician marked events and algorithm marked events. In the physicianmarking embodiment, the loop recording stored data must be uplinked toan external device such as a programmer or other computer. Uponuplinking the loop recording stored data, the physician may score theonset, offset or other reference points in the EEG signal at block 876.The physician may also classify the events as seizure related or not. Amatching test (EEG detections versus ECG or respiratory detections) isexecuted at block 877. The EEG inputs to the matching test may be eitherphysician scores (e.g., onset, offset of seizure) or the automatedscores from the neurological event detection algorithm. The matchingtest results from block 877 result in a summary of comparisons madebetween the EEG and ECG detections (or between the EEG and respiratorydetections). At block 878 the matching test results are evaluated. Theevaluation at block 878 includes blocks 879, 880 and 881 (i.e., blocks879, 880 and 881 are components of block 878. At block 879 concordancebetween EEG and ECG/respiratory detections is determined. At block 880an ECG false positive rate (relative to the neurological signal) isevaluated using the un-matched events in the ECG or respiratory signals.At block 881 ECG/respiratory latency is evaluated for the matcheddetections. At block 882, seizure detection improvement using ECG orrespiration signals is considered based upon the above determinations.If use of ECG signals or respiratory signals does not improve seizuredetection (“NO” condition), then the physician or other user maymaintain or disable the ECG algorithm monitoring at block 883. Themonitor begins monitoring or treatment at block 885. If at block 882 theresult is YES, the ECG or respiratory signal is activated for seizuremonitoring.

Monitor+Treatment (Brain)

FIG. 41 is a block diagram of the electronic circuitry that makes upfull Monitor/Brain Therapy device 300 (FIG. 11) in accordance with thepresently disclosed alternative embodiment of the invention. As can beseen from FIG. 41, Monitor/Brian Therapy device 300 comprises a primarycontrol circuit 720 that is described herein above in conjunction withFIG. 26. In addition the Monitor/Brain Therapy device 300 of FIG. 41also includes an amplifier 725 to amplify and sense EEG signals from acranially implanted lead (one embodiment of a brain monitoring element18) and a therapy module for providing therapy to the brain. The therapymodule may be a drug delivery pump or an electrical stimulator or abrain cooling mechanism or other components depending on the treatmentmodality. In the embodiment of FIG. 41, the therapy module is an outputstimulator 729 for stimulation of the brain. The CPU 732, in conjunctionwith software program in RAM/ROM 730, integrates the information fromthe sensed cardiac, respiration and EEG signals, detects the onset ofcerebral, cardiac or respiratory anomalies, provides preprogrammedstimulation therapy to the patient's brain via a brain lead that may bethe same as monitoring element 18, formats and stores diagnostic datafor later retrieval by the patient's clinician and, optionally, may warnor alert the patient, patient caregiver or remote monitoring location.See flow diagram and description as described below in association withFIG. 56.

FIG. 42 is a block diagram of the electronic circuitry that makes upfull Monitor/Brain Therapy device 320 (FIG. 12A) in accordance with thepresently disclosed alternative embodiment of the invention. As can beseen from FIG. 42, Monitor/Brain Therapy device 320 comprises a primarycontrol circuit 720 and MV circuit 722 that are described herein abovein conjunction with FIG. 28. In addition the Monitor/Brain Therapydevice of FIG. 42 also includes an amplifier 725 to amplify and senseEEG signals from a cranially implanted monitoring element 18 and anoutput stimulator 729 to provide brain stimulation. The CPU 732, inconjunction with software program in RAM/ROM 730, integrates theinformation from the sensed cardiac, respiration and EEG signals,detects the onset of cerebral, cardiac or respiratory anomalies,provides preprogrammed stimulation therapy to the patient's brain via alead that may be the same as brain monitoring element 18, formats andstores diagnostic data for later retrieval by the patient's clinicianand, optionally, may warn or alert the patient, patient caregiver orremote monitoring location. See flow diagram and description asdescribed below in association with FIG. 56.

FIG. 43 is a block diagram of the electronic circuitry that makes upfull Monitor/Brain Therapy device 321 (FIG. 12B) in accordance with thepresently disclosed alternative embodiment of the invention. As can beseen from FIG. 43, Monitor/Brain Therapy device 321 in combination witha cranially implanted Monitor/Brain Therapy unit 26 in a patient 10includes a primary control circuit 720 and MV circuit 722 that aredescribed herein above in conjunction with FIG. 28. A 2-way wirelesstelemetry communication link 30 connects the Monitor/Therapy unit 26 andMonitor/Brain Therapy unit 321 via antennas 736. The wirelesscommunication link 30 may consist of an RF link (such as described inU.S. Pat. No. 5,683,432 “Adaptive Performance-Optimizing CommunicationSystem for Communicating with an Implantable Medical Device” to Goedeke,et al, an electromagnetic/ionic transmission (such as described in U.S.Pat. No. 4,987,897 “Body Bus Medical Device Communication System” toFunke) or acoustic transmission (such as described in U.S. Pat. No.5,113,859 “Acoustic Body Bus Medical Device Communication System” toFunke). Monitor/Brain Therapy unit 26 contains an amplifier 725 toamplify and sense EEG signals from a cranially implanted brainmonitoring element 18 such as a lead and an output stimulator 729 forstimulation of the brain. Monitor 26 may be constructed as substantiallydescribed in US Publication No. 20040176817 “Modular implantable medicaldevice” to Wahlstrand et al. or U.S. Pat. No. 5,782,891 “ImplantableCeramic Enclosure for Pacing, Neurological and Other MedicalApplications in the Human Body” to Hassler, et al or U.S. Pat. No.6,427,086 “Means and Method for the Intracranial Placement of aNeurostimulator” to Fischell. et al. EEG sensing is accomplished by theuse of integrated electrodes in the housing of monitor 26 or,alternatively, by a brain monitoring element 18 such as a craniallyimplanted leads.

Specifically, CPU 732, in conjunction with software program in RAM/ROM730, integrates the information from the sensed cardiac, respiration andEEG signals, detects the onset of cerebral, cardiac or respiratoryanomalies, provides preprogrammed stimulation therapy to the patient'sbrain via a lead or other therapy delivery device (that could be thesame as brain monitoring element 18), formats and stores diagnostic datafor later retrieval by the patient's clinician and, optionally, may warnor alert the patient, patient caregiver or remote monitoring location.See flow diagram and description as described below in association withFIG. 56.

FIG. 44 is a block diagram of one embodiment of the electronic circuitrythat makes up full Monitor/Brain Therapy device 340 with a brainmonitoring element 18 (e.g., lead) and cardiac or respiratory monitoringelement 14 such as sensor stub 20 (FIG. 13) in accordance with thepresently disclosed alternative embodiment of the invention. As can beseen from FIG. 44, Monitor/Brain Therapy device 340 comprises a primarycontrol circuit 720 and MV circuit 722 that were described herein abovein conjunction with FIG. 28. In addition, the full Monitor/Brain Therapydevice 340 of FIG. 44 also includes an amplifier 725 to amplify andsense EEG signals from a brain monitoring element 18 such as a craniallyimplanted lead. Additionally, the full Monitor/Brain Therapy device 340of FIG. 44 also includes a stimulator 729 for providing stimulation tothe brain through brain monitoring element 18 such as a craniallyimplanted lead. The CPU 732, in conjunction with a software programresident in RAM/ROM 730, integrates the information from the sensedcardiac, respiration and EEG signals, detects the onset of cerebral,cardiac or respiratory anomalies, provides preprogrammed stimulationtherapy to the patient's brain via a therapeutic element such as brainmonitoring element 18 which may be a lead, formats and stores diagnosticdata for later retrieval by the patient's clinician and, optionally, maywarn or alert the patient, patient caregiver or remote monitoringlocation. See flow diagram and description as described below inassociation with FIG. 56.

FIG. 45 is a block diagram of one embodiment of the electronic circuitrythat makes up external patch 160/full Monitor/Brain Therapy device 360with a brain monitoring element 18 that may be used for sensing andapplication of therapy (in the case of therapy being electricalstimulation) (FIG. 8) in accordance with the presently disclosedalternative embodiment of the invention. As can be seen from FIG. 45,Monitor/Brain Therapy device 360 comprises a primary control circuit 720and external patch comprises a cardiac/MV (minute ventilation) circuit160, the functions of which have been described in detail above inconjunction with the system of FIG. 28. Intrinsic cardiac signals aresensed by electrodes affixed to the patient's skin, amplified byamplifier 724, sent to primary control circuit 720 and processed by CPU732 and software program resident in RAM/ROM 730. Cardiac anomalies aredetected such as heart rate variability, QT variability, QT_(C), sinusarrest, and various arrhythmias such as sinus, atrial and ventriculartachycardias. Respiration sensing is accomplished by low pass filteringthe sensed and amplified intrinsic cardiac signals as shown in FIG. 27or, alternatively, by using the MV/Z measurement circuitry of externalpatch 160 as described above in connection with FIG. 28. Respirationanomalies (such as reduced or cessation of tidal volume and apnea) areevaluated and detected by CPU 732 and software resident in RAM/ROM 730.

The CPU 732, in conjunction with a software program resident in RAM/ROM730, integrates the information from the sensed cardiac, respiration andEEG signals, detects the onset of cerebral, cardiac or respiratoryanomalies, provides preprogrammed stimulation therapy to the patient'sbrain via lead 18, formats and stores diagnostic data for laterretrieval by the patient's clinician and, optionally, may warn or alertthe patient, patient caregiver or remote monitoring location. See flowdiagram and description as described below in association with FIG. 56.

The circuitry and function of the device 340 shown in FIG. 44 anddescribed herein above may also be used for the full Monitor/BrainTherapy device 380 with integrated electrode 24 brain lead 18 (FIG. 15).As described above in association with core Monitor 340, thoracicimpedance via impedance/voltage converter as measured from the case ofmonitor 340 to the integrated electrode 24 using a sampling frequency ofapproximately. 16 Hz as substantially described in U.S. Pat. No.4,596,251 “Minute Ventilation Dependant Rate Responsive Pacer” toPlicchi, et al. The Monitor 380 of this alternative embodiment utilizesthe same circuitry of Monitor 340 but connected to the integratedelectrode 24 on brain lead 18 instead of the sensor stub of Monitor 340.

Upon detection of either/or a cardiac or respiration anomaly, CPU 732,under control of firmware resident in RAM/ROM 730, will initiaterecording of the appropriate diagnostic information into RAM of RAM/ROM730, provides preprogrammed stimulation therapy to the patient's brainvia lead 18, formats and stores diagnostic data for later retrieval bythe patient's clinician and, optionally, may warn or alert the patient,patient caregiver or remote monitoring location. See flow diagram anddescription as described below in association with FIG. 56.

FIG. 46 is a block diagram of the electronic circuitry that makes upfull Monitor/Brain Therapy device 400 (FIG. 20) in accordance with thepresently disclosed alternative embodiment of the invention. As can beseen from FIG. 46, Monitor/Brian Therapy device 400 comprises a primarycontrol circuit 720 (sensing cardiac and respiration parameters) that isdescribed herein above in conjunction with FIG. 26. In addition theMonitor/Brain Therapy device 400 connects via a 2-way wirelesscommunication link 30 to a cranially implanted EEG sensor and brainstimulator 26. EEG senor and brain stimulator 26 contains an amplifier725 to amplify and sense EEG signals from a cranially implanted lead 18and an output stimulator 729 for stimulation of the brain. The CPU 732,in conjunction with software program in RAM/ROM 730, integrates theinformation from the sensed cardiac, respiration and EEG signals,detects the onset of cerebral, cardiac or respiratory anomalies,provides preprogrammed stimulation therapy to the patient's brain vialead 18, formats and stores diagnostic data for later retrieval by thepatient's clinician and, optionally, may warn or alert the patient,patient caregiver or remote monitoring location. See flow diagram anddescription as described below in association with FIG. 56.

FIG. 47 is a block diagram of the electronic circuitry that makes upfull Monitor/Brain Therapy device 420 (FIG. 21) in accordance with thepresently disclosed alternative embodiment of the invention. As can beseen from FIG. 47, Monitor/Brian Therapy device 420 comprises a primarycontrol circuit 720 (sensing cardiac and respiration parameters) that isconfigured as an external patch affixed to a patient and whose functionis described herein above in conjunction with FIG. 26. In addition, theMonitor/Brain Therapy device 420 comprises to a cranially implanted EEGsensor and brain stimulator 26 connected to the primary control circuit720 via a 2-way wireless communication link 30. The wirelesscommunication link 30 may consist of an RF link (such as described inU.S. Pat. No. 5,683,432 “Adaptive Performance-Optimizing CommunicationSystem for Communicating with an Implantable Medical Device” to Goedeke,et al.), an electromagnetic/ionic transmission (such as described inU.S. Pat. No. 4,987,897 “Body Bus Medical Device Communication System”to Funke) or acoustic transmission (such as described in U.S. Pat. No.5,113,859 “Acoustic Body Bus Medical Device Communication System” toFunke). EEG sensor and brain stimulator 26 contains an amplifier 725 toamplify and sense EEG signals from a cranially implanted lead 18 and anoutput stimulator 729 for stimulation of the brain. The CPU 732, inconjunction with software program in RAM/ROM 730, integrates theinformation from the sensed cardiac, respiration and EEG signals,detects the onset of cerebral, cardiac or respiratory anomalies,provides preprogrammed stimulation therapy to the patient's brain vialead 18, formats and stores diagnostic data for later retrieval by thepatient's clinician and, optionally, may warn or alert the patient,patient caregiver or remote monitoring location. See flow diagram anddescription as described below in association with FIG. 56.

Monitor+Treatment (Brain+Respiration)

FIG. 48 is a block diagram of the electronic circuitry that makes upfull Monitor/Brain and Respiration Therapy device 440 (FIG. 16A) inaccordance with the presently disclosed alternative embodiment of theinvention. As can be seen from FIG. 48, Monitor/Brain and RespirationTherapy device 440 comprises a primary control circuit 720 and MVcircuit 722 whose function was described herein above in conjunctionwith FIG. 28. In addition the Monitor/Brain and Respiration Therapydevice of FIG. 48 also includes an amplifier 725 to amplify and senseEEG signals from a cranially implanted lead 18 and an output stimulator729 to provide brain stimulation via cranially implanted lead 18 andphrenic nerve stimulation via respiration lead 28. The CPU 732, inconjunction with software program in RAM/ROM 730, integrates theinformation from the sensed cardiac, respiration and EEG signals,detects the onset of cerebral, cardiac or respiratory anomalies,provides preprogrammed stimulation therapy to the patient's brain vialead 18 and stimulation of the patient's phrenic nerve via respirationlead 28, formats and stores diagnostic data for later retrieval by thepatient's clinician and, optionally, may warn or alert the patient,patient caregiver or remote monitoring location. Optionally, lead 28 mayconnect to the diaphragm to provide direct diaphragmatic stimulation.See flow diagram and description as described below in association withFIG. 56.

FIG. 49 is a block diagram of the electronic circuitry that makes upfull Monitor/Brain and Respiration Therapy device 441 (FIG. 16B) inaccordance with the presently disclosed alternative embodiment of theinvention. As can be seen from FIG. 49, Monitor/Brain and RespirationTherapy device 441 in combination with a cranially implantedMonitor/Brain Therapy unit 26 in a patient 10 includes a primary controlcircuit 720 and MV circuit 722 that are described herein above inconjunction with FIG. 28. A 2-way wireless telemetry communication link30 connects the Monitor/Therapy unit 26 and Monitor/Brain andRespiration Therapy unit 441 via antennas 736. The wirelesscommunication link 30 may consist of an RF link (such as described inU.S. Pat. No. 5,683,432 “Adaptive Performance-Optimizing CommunicationSystem for Communicating with an Implantable Medical Device” to Goedeke,et al), an electromagnetic/ionic transmission (such as described in U.S.Pat. No. 4,987,897 “Body Bus Medical Device Communication System” toFunke) or acoustic transmission (such as described in U.S. Pat. No.5,113,859 “Acoustic Body Bus Medical Device Communication System” toFunke). Monitor/Brain Therapy unit 26 contains an amplifier 725 toamplify and sense EEG signals from a cranially implanted lead 18 and anoutput stimulator 729 for stimulation of the brain. Monitor 26 may beconstructed as substantially described in US Publication No. 20040176817“Modular implantable medical device” to Wahlstrand et al. or U.S. Pat.Nos. 5,782,891 “Implantable Ceramic Enclosure for Pacing, Neurologicaland Other Medical Applications in the Human Body” to Hassler, et al orU.S. Pat. No. 6,427,086 “Means and Method for the Intracranial Placementof a Neurostimulator” to Fischell. et al. EEG sensing is accomplished bythe use of integrated electrodes in the housing of monitor 26 or,alternatively, by cranially implanted leads 18.

Specifically, CPU 732, in conjunction with software program in RAM/ROM730, integrates the information from the sensed cardiac, respiration andEEG signals, detects the onset of cerebral, cardiac or respiratoryanomalies, provides preprogrammed stimulation therapy to the patient'sbrain via lead 18 and to the phrenic nerve via respiration lead 28,formats and stores diagnostic data for later retrieval by the patient'sclinician and, optionally, may warn or alert the patient, patientcaregiver or remote monitoring location. Optionally, lead 28 may connectto the diaphragm to provide direct diaphragmatic stimulation. See flowdiagram and description as described below in association with FIG. 56.

FIG. 50 is a block diagram of the electronic circuitry that makes upfull Monitor/Brain and Respiration Therapy device 460 with a brain lead18, phrenic nerve lead 28 and sensor stub 20 (FIG. 17) in accordancewith the presently disclosed alternative embodiment of the invention. Ascan be seen from FIG. 50, Monitor/Brain and Respiration Therapy device460 comprises a primary control circuit 720 and MV circuit 722 whosefunction was described herein above in conjunction with FIG. 28. Inaddition, the full Monitor/Brain and Respiration Therapy device 460 ofFIG. 50 also includes an amplifier 725 to amplify and sense EEG signalsfrom a cranially implanted lead 18. Additionally, the full Monitor/BrainTherapy device 340 of FIG. 44 also includes a stimulator 729 forproviding stimulation to the brain through cranially implanted lead 18and phrenic nerve stimulation via respiration lead 28. The CPU 732, inconjunction with a software program resident in RAM/ROM 730, integratesthe information from the sensed cardiac, respiration and EEG signals,detects the onset of cerebral, cardiac or respiratory anomalies,provides preprogrammed stimulation therapy to the patient's brain vialead 18 and stimulation of the patient's phrenic nerve via respirationlead 28, formats and stores diagnostic data for later retrieval by thepatient's clinician and, optionally, may warn or alert the patient,patient caregiver or remote monitoring location. See flow diagram anddescription as described below in association with FIG. 56.

The circuitry and function of the device 460 shown in FIG. 50 anddescribed herein above may also be used for the full Monitor/Brain andRespiration Therapy device 480 with integrated electrode 24 brain lead18 and phrenic nerve lead 28 (FIG. 18). As described above inassociation with Monitor/Brain and Respiration Therapy device 460,thoracic impedance via impedance/voltage converter as measured from thecase of monitor 480 to the integrated electrode 24 using a samplingfrequency of approximately 16 Hz as substantially described in U.S. Pat.No. 4,596,251 “Minute Ventilation Dependant Rate Responsive Pacer” toPlicchi, et al. The Monitor/Brain and Respiration Therapy device 480 ofthis alternative embodiment utilizes the same circuitry of Monitor/Brainand Respiration Therapy device 460 but connected to the integratedelectrode 24 on brain lead 18 instead of the sensor stub 20 ofMonitor/Brain and Respiration Therapy device 340.

Upon detection of either/or a cardiac or respiration anomaly, CPU 732,under control of firmware resident in RAM/ROM 730, will initiaterecording of the appropriate diagnostic information into RAM of RAM/ROM730, provides preprogrammed stimulation therapy to the patient's brainvia lead 18 and stimulation of the patient's phrenic nerve viarespiration lead 28, formats and stores diagnostic data for laterretrieval by the patient's clinician and, optionally, may warn or alertthe patient, patient caregiver or remote monitoring location. See flowdiagram and description as described below in association with FIG. 56.

The circuitry and function of the device 460 shown in FIG. 50 anddescribed herein above may also be used for the full Monitor/Brain andRespiration Therapy device 500 with brain lead 18 and integratedelectrode 24 phrenic nerve lead 28 (FIG. 19). As described above inassociation with Monitor/Brain and Respiration Therapy device 460,thoracic impedance via impedance/voltage converter as measured from thecase of monitor 500 to the integrated electrode 24 using a samplingfrequency of approximately 16 Hz as substantially described in U.S. Pat.No. 4,596,251 “Minute Ventilation Dependant Rate Responsive Pacer” toPlicchi, et al. The Monitor/Brain and Respiration Therapy device 500 ofthis alternative embodiment utilizes the same circuitry of Monitor/Brainand Respiration Therapy device 460 but connected to the integratedelectrode 24 on phrenic nerve lead 28 instead of the sensor stub 20 ofMonitor/Brain and Respiration Therapy device 340.

Upon detection of either/or a cardiac or respiration anomaly, CPU 732,under control of firmware resident in RAM/ROM 730, will initiaterecording of the appropriate diagnostic information into RAM of RAM/ROM730, provides preprogrammed stimulation therapy to the patient's brainvia lead 18 and stimulation of the patient's phrenic nerve viarespiration lead 28, formats and stores diagnostic data for laterretrieval by the patient's clinician and, optionally, may warn or alertthe patient, patient caregiver or remote monitoring location. See flowdiagram and description as described below in association with FIG. 56.

Monitor+Treatment (Brain+Cardiac)

FIG. 51 is a block diagram of the electronic circuitry that makes upfull Monitor/Brain and Cardiac Therapy device 520 (FIG. 24A) inaccordance with the presently disclosed alternative embodiment of theinvention. As can be seen from FIG. 51, Monitor/Brain and CardiacTherapy device 520 comprises a primary control circuit 720 and MVcircuit 722 whose function is described herein above in conjunction withFIG. 28 and U.S. Pat. No. 5,271,395 “Method and Apparatus for RateResponsive Cardiac Pacing” to Wahlstrand et al. In addition, theMonitor/Brain and Cardiac Therapy device of FIG. 51 also includes anamplifier 725 to amplify and sense EEG signals from a craniallyimplanted lead 18 and an output stimulator 729 to provide brainstimulation. The CPU 732, in conjunction with software program inRAM/ROM 730, integrates the information from the sensed cardiac,respiration and EEG signals, detects the onset of cerebral, cardiac orrespiratory anomalies, provides preprogrammed stimulation therapy to thepatient's brain via lead 18 and stimulation to the patient's heart viacardiac lead(s) 16, formats and stores diagnostic data for laterretrieval by the patient's clinician and, optionally, may warn or alertthe patient, patient caregiver or remote monitoring location. See flowdiagram and description as described below in association with FIG. 54.

FIG. 52 is a block diagram of the electronic circuitry that makes upfull Monitor/Brain and Cardiac Therapy device 521 (FIG. 24B) inaccordance with the presently disclosed alternative embodiment of theinvention. As can be seen from FIG. 52, Monitor/Brain and CardiacTherapy device 521 in combination with a cranially implantedMonitor/Brain Therapy unit 26 in a patient 10 includes a primary controlcircuit 720 and MV circuit 722 that are described herein above inconjunction with FIG. 28. A 2-way wireless telemetry communication link30 connects the Monitor/Therapy unit 26 and Monitor/Brain and CardiacTherapy unit 521 via antennas 736. The wireless communication link 30may consist of an RF link (such as described in U.S. Pat. No. 5,683,432“Adaptive Performance-Optimizing Communication System for Communicatingwith an Implantable Medical Device” to Goedeke, et al), anelectromagnetic/ionic transmission (such as described in U.S. Pat. No.4,987,897 “Body Bus Medical Device Communication System” to Funke) oracoustic transmission (such as described in U.S. Pat. No. 5,113,859“Acoustic Body Bus Medical Device Communication System” to Funke).Monitor/Brain Therapy unit 26 contains an amplifier 725 to amplify andsense EEG signals from a cranially implanted lead 18 and an outputstimulator 729 for stimulation of the brain. Monitor 26 may beconstructed as substantially described in US Publication No. 20040176817“Modular implantable medical device” to Wahlstrand et al. or U.S. Pat.No. 5,782,891 “Implantable Ceramic Enclosure for Pacing, Neurologicaland Other Medical Applications in the Human Body” to Hassler, et al orU.S. Pat. No. 6,427,086 “Means and Method for the Intracranial Placementof a Neurostimulator” to Fischell. et al. EEG sensing is accomplished bythe use of integrated electrodes in the housing of monitor 26 or,alternatively, by cranially implanted leads 18.

Specifically, CPU 732, in conjunction with software program in RAM/ROM730, integrates the information from the sensed cardiac, respiration andEEG signals, detects the onset of cerebral, cardiac or respiratoryanomalies, provides preprogrammed stimulation therapy to the patient'sbrain via lead 18 and cardiac stimulation via cardiac leads 16, formatsand stores diagnostic data for later retrieval by the patient'sclinician and, optionally, may warn or alert the patient, patientcaregiver or remote monitoring location. See flow diagram anddescription as described below in association with FIG. 56.

Alternatively, the device as described above in connection to theMonitor and Treatment (Brain and Cardiac) system of FIG. 52 may includea pacemaker/cardioverter/defibrillator (PCD) to enable the terminationof cardiac arrhythmias during, or prior to, neurological events. The PCDmay be of the type as substantially described in U.S. Pat. No. 5,545,186“Prioritized Rule Based Method and Apparatus for Diagnosis and Treatmentof Arrhythmias” to Olson; U.S. Pat. No. 5,354,316 “Method and Apparatusfor Detection and Treatment of Tachycardia and fibrillation” to Kiemelor U.S. Pat. No. 5,314,430 “Atrial Defibrillator Employing Transvenousand Subcutaneous Electrodes and Method of Use” to Bardy. In oneembodiment of the present invention, the PCD arrhythmia detectioncircuitry/algorithms are enabled upon the sensing of the onset orimpending onset of a seizure. Upon seizure termination, the arrhythmiadetection circuitry/algorithms are turned off.

FIG. 53 is a block diagram of the electronic circuitry that makes upfull Monitor/Brain and Cardiac Therapy device 540 (FIG. 22) inaccordance with the presently disclosed alternative embodiment of theinvention. The system as shown in FIG. 53 is used for patientstemporarily at risk of sudden death, for example, while the patient'sphysician is trying different epileptic drugs and titrating dosages toeliminate/minimize seizures or their severity. As can be seen from FIG.53, Monitor/Brain and Cardiac Therapy device 540 comprises patient wornvest defibrillator 34 containing primary control circuit 720 whosefunction is described herein above in conjunction with FIG. 26 and inmore detail in U.S. Pat. No. 6,280,461 “Patient-Worn Energy DeliveryApparatus” to Glegyak, et. In addition the Monitor/Brain and CardiacTherapy device connects via a 2-way wireless communication link 30 to acranially implanted brain stimulator 540. The wireless communicationlink 30 may consist of an RF link (such as described in U.S. Pat. No.5,683,432 “Adaptive Performance-Optimizing Communication System forCommunicating with an Implantable Medical Device” to Goedeke, et al), anelectromagnetic/ionic transmission (such as described in U.S. Pat. No.4,987,897 “Body Bus Medical Device Communication System” to Funke) oracoustic transmission (such as described in U.S. Pat. No. 5,113,859“Acoustic Body Bus Medical Device Communication System” to Funke). EEGsenor and brain stimulator 540 contains an amplifier 725 to amplify andsense EEG signals from a cranially implanted lead 18 and an outputstimulator 729. The CPU 732, in conjunction with software program inRAM/ROM 730, integrates the information from the sensed cardiac,respiration and EEG signals, detects the onset of cerebral, cardiac orrespiratory anomalies, provides preprogrammed stimulation therapy to thepatient's brain via lead 18 and defibrillation therapy via patient wornvest 34, formats and stores diagnostic data for later retrieval by thepatient's clinician and, optionally, may warn or alert the patient,patient caregiver or remote monitoring location. See flow diagram anddescription as described below in association with FIG. 56.

The circuitry and function of the device 540 shown in FIG. 53 anddescribed herein above may also be used for the full Monitor/Brain andCardiac Therapy device 560 with a cranially implanted stimulator in2-way communication with an leadless subcutaneous implantabledefibrillator 36 (ie, “lifeboat”, FIG. 23). The system described inconnection with this embodiment is used for patients temporarily at riskof sudden death, for example, while the patient's physician is tryingdifferent epileptic drugs and titrating dosages to eliminate/minimizeseizures or their severity. As described above in conjunction with FIG.53, Monitor/Brian and Cardiac Therapy device 560 comprises a leadlessdefibrillator 36 containing primary control circuit 720 whose functionis described herein above in conjunction with FIG. 26 and in more detailin U.S. Pat. No. 6,647,292 “Unitary Subcutaneous only ImplantableCardioverter-Defibrillator and Optional Pacer” to Bardy.

The Monitor/Brain and Cardiac Therapy device connects via a 2-waywireless communication link 30 to a cranially implanted brain stimulator560. The wireless communication link 30 may consist of an RF link (suchas described in U.S. Pat. No. 5,683,432 “Adaptive Performance-OptimizingCommunication System for Communicating with an Implantable MedicalDevice” to Goedeke, et al), an electromagnetic/ionic transmission (suchas described in U.S. Pat. No. 4,987,897 “Body Bus Medical DeviceCommunication System” to Funke) or acoustic transmission (such asdescribed in U.S. Pat. No. 5,113,859 “Acoustic Body Bus Medical DeviceCommunication System” to Funke). EEG senor and brain stimulator 560contains an amplifier 725 to amplify and sense EEG signals from acranially implanted lead 18 and an output stimulator 729. The CPU 732,in conjunction with software program in RAM/ROM 730, integrates theinformation from the sensed cardiac, respiration and EEG signals,detects the onset of cerebral, cardiac or respiratory anomalies,provides preprogrammed stimulation therapy to the patient's brain vialead 18 and defibrillation therapy via implanted defibrillator 36,formats and stores diagnostic data for later retrieval by the patient'sclinician and, optionally, may warn or alert the patient, patientcaregiver or remote monitoring location. See flow diagram anddescription as described below in association with FIG. 56.

Monitor+Treatment (Brain+Respiration+Cardiac)

FIG. 54 is a block diagram of the electronic circuitry that makes upfull Monitor/Brain, Respiration and Cardiac Therapy device 580 (FIG.25A) in accordance with the presently disclosed alternative embodimentof the invention. As can be seen from FIG. 54, Monitor/Brain,Respiration and Cardiac Therapy device 580 comprises a primary controlcircuit 720 and MV circuit 722 whose function was described herein abovein conjunction with FIG. 28. In addition the Monitor/Brain, Respirationand Cardiac Therapy device of FIG. 54 also includes an amplifier 725 toamplify and sense EEG signals from a cranially implanted lead 18 and anoutput stimulator 729 to provide brain stimulation via craniallyimplanted lead 18 and phrenic nerve stimulation via respiration lead 28.The CPU 732, in conjunction with software program in RAM/ROM 730,integrates the information from the sensed cardiac, respiration and EEGsignals, detects the onset of cerebral, cardiac or respiratoryanomalies, provides preprogrammed stimulation therapy to the patient'sbrain via lead 18, stimulation of the patient's phrenic nerve viarespiration lead 28 and stimulation of the patient's heart via cardiacleads 16, formats and stores diagnostic data for later retrieval by thepatient's clinician and, optionally, may warn or alert the patient,patient caregiver or remote monitoring location. Optionally, lead 28 mayconnect to the diaphragm to provide direct diaphragmatic stimulation.See flow diagram and description as described below in association withFIG. 56.

FIG. 55 is a block diagram of the electronic circuitry that makes upfull Monitor/Brain, Respiration and Cardiac Therapy device 581 (FIG.25B) in accordance with the presently disclosed alternative embodimentof the invention. As can be seen from FIG. 55, Monitor/Brain,Respiration and Cardiac Therapy device 581 in combination with acranially implanted Monitor/Brain Therapy unit 26 in a patient 10includes a primary control circuit 720 and MV circuit 722 that aredescribed herein above in conjunction with FIG. 28. A 2-way wirelesstelemetry communication link 30 connects the Monitor/Therapy unit 26 andMonitor/Brain, Respiration and Cardiac Therapy unit 581 via antennas736. The wireless communication link 30 may consist of an RF link (suchas described in U.S. Pat. No. 5,683,432 “Adaptive Performance-OptimizingCommunication System for Communicating with an Implantable MedicalDevice” to Goedeke, et al), an electromagnetic/ionic transmission (suchas described in U.S. Pat. No. 4,987,897 “Body Bus Medical DeviceCommunication System” to Funke) or acoustic transmission (such asdescribed in U.S. Pat. No. 5,113,859 “Acoustic Body Bus Medical DeviceCommunication System” to Funke). Monitor/Brain Therapy unit 26 containsan amplifier 725 to amplify and sense EEG signals from a craniallyimplanted lead 18 and an output stimulator 729 for stimulation of thebrain. Monitor 26 may be constructed as substantially described in USPublication No. 20040176817 “Modular implantable medical device” toWahlstrand et al. or U.S. Pat. No. 5,782,891 “Implantable CeramicEnclosure for Pacing, Neurological and Other Medical Applications in theHuman Body” to Hassler, et al or U.S. Pat. No. 6,427,086 “Means andMethod for the Intracranial Placement of a Neurostimulator” to Fischell.et al. EEG sensing is accomplished by the use of integrated electrodesin the housing of monitor 26 or, alternatively, by cranially implantedleads 18.

Specifically, CPU 732, in conjunction with software program in RAM/ROM730, integrates the information from the sensed cardiac, respiration andEEG signals, detects the onset of cerebral, cardiac or respiratoryanomalies, provides preprogrammed stimulation therapy to the patient'sbrain via lead 18, to the phrenic nerve via respiration lead 28 and tothe heart via cardiac leads 16, formats and stores diagnostic data forlater retrieval by the patient's clinician and, optionally, may warn oralert the patient, patient caregiver or remote monitoring location.Optionally, lead 28 may connect to the diaphragm to provide directdiaphragmatic stimulation. See flow diagram and description as describedbelow in association with FIG. 56.

FIG. 56 is a flow diagram 850 showing operation of a fullmonitor/therapy sensing and monitoring cardiac, respiration andelectroencephalogram parameters for the detection of neurological eventsas shown and described in embodiments in FIG. 11-25 above. The blocks802-808 relating to the identification of cardiac activity, and blocks816-822 relating to identification of respiratory activity, may beactivated or deactivated according to the determination of whether theyimprove the detection of the neurological disorder (see for example thediscussion regarding determining concordance). It is noted that theparticular detection scheme used for each of the physiologic signals(brain, heart, respiratory) is not restricted to the examples providedhere.

In one embodiment, beginning at block 802, the interval between sensedcardiac signals are measured. At block 804, a rate stability measurementis made on each cardiac interval utilizing a heart rate average fromblock 806. At block 808, a rate stable decision is made based uponpreprogrammed parameters. If YES (heart rate is determined to bestable), the flow diagram returns to the HR Measurement block 802. IfNO, the rate stability information is provided to Determine Therapy andDuration block 830.

At block 816, thoracic impedance is continuously measured in a samplingoperation. At block 818, a MV and respiration rate calculation is made.At block 822, a pulmonary apnea decision is made based uponpreprogrammed criteria. If NO (no apnea detected), the flow diagramreturns to MV Measurement block 816. If YES, the occurrence of apnea andMV information is provided to Determine Therapy and Duration block 830.

At block 824, the electroencephalogram is sensed and measured. An EEGcalculation is performed at block 826. The seizure detection algorithmis executed at block 826. At block 828, a seizure episode is determined.If NO (no seizure detected), the flow diagram returns to EEG Measurementblock 824. If YES, the occurrence of a seizure is provided to DetermineTherapy and Duration block 830.

Based upon the data presented to it, Determine Therapy and Durationblock 830 determines the type of therapy and the duration to block 832,which controls the start of the therapy by evaluating the severity andranking of each event (i.e., maximum ratio, duration of seizuredetection, spread, number of clusters per unit time, number ofdetections per cluster, duration of an event cluster, duration of adetection, and inter-seizure interval) per co-pending U.S. patentapplication Publication No. 20040133119 “Scoring of sensed neurologicalsignals for use with a medical device system”

to Osorio, et al incorporated herein by reference in its entirety. Block834 monitors the completion of the determined therapy. If the therapy isnot complete, control returns to block 834. If the therapy is determinedto be complete, block 834 returns the flow diagram to blocks 802(Measure HR), 816 (Measure Impedance) and 824 (Measure EEG) to continuethe monitoring of cardiac, respiratory and brain signal parameters.

Therapy may consist of neural stimulation, cardiac pacing,cardioversion/defibrillation, and drug delivery via a pump, braincooling, or any combination of therapies.

When block 830 determines that a therapy is to be initiated FormatDiagnostic Data block 812 formats the data from the cardiac, respirationand EEG monitoring channels, adds a time stamp (ie, date and time), typeand duration of therapy and provides the data to block 814 where thedata is stored in RAM memory for later retrieval by a clinician viatelemetry. Optionally, block 812 may add examples of intrinsic ECG,respiration or EEG signals recorded during a sensed episode/seizure.

The physician may program the devices shown above in relation to FIGS.11-25 and 41-55 to allow the ECG/respiratory detectors be enabled totrigger the delivery of therapy (i.e., stimulation or drug delivery) tothe patient's brain, with goal of aborting seizures earlier or limitingtheir severity than if using EEG signal detection alone. Either EEG,respiratory or ECG detections may trigger therapy to the brain,depending on which occurs first. The physician may choose the type ofECG or respiratory event to use for triggering therapy to the brain.

Application of Therapy to the Brain Based on Cardiac or RespiratorySignals and Termination of Such Therapy

In the present invention of the devices shown above in relation to FIGS.11-25 and 41-55, the device is able to terminate or change thecardiac/respiratory initiated treatment, directed at the brain, if aneurological event is not entered within an expected time framefollowing cardiac detection. This feature allows the device to begintreating a patient's neurological event before its detection in thebrain signal. These termination conditions are defined at block 990 ofFIG. 40A and 890 of FIG. 40B.

If the cardiac/respiratory initiated brain therapy has been ongoing forsome time, and polling of the brain signal (i.e., processing the brainsignal with a neurological event detection algorithm) has indicated thepatient is not in a neurological event, then the following may be true:

-   1. Cardiac/respiratory triggered therapy was successful in aborting    the neurological event, and therefore, the neurological event is not    detectable in the brain signal.-   2. The cardiac/respiratory event was not associated with a    neurological event.

In either case, it would be appropriate to change (adjust or terminate)cardiac/respiratory initiated therapy directed specifically at abortinga neurological event. FIG. 57A is a flow chart illustrating theprocessing steps executed by a processor (e.g., CPU 732 or any otherprocessor). At block 1000 the processor monitors the cardiac orrespiratory signals or both. At block 1002, the processor detects acardiac or respiratory event in the cardiac or respiratory signals.Based upon a cardiac or respiratory event detection at block 1002, theprocessor activates the therapy module to provide therapy to the brainat block 1004. The brain signal is monitored at block 1006. This may bea continuation of monitoring of the brain that was already ongoing or itmay be initiation of brain monitoring. Once the therapy has beeninitiated from a cardiac or respiratory detection, the therapy may bechanged at block 1008 based on the monitoring of the brain signal.

One embodiment of the process of FIG. 57A is illustrated in FIG. 57B.The processor receives the cardiac or respiratory signals at block 1050.A cardiac or respiratory event is detected at block 1052. The therapymodule is activated at block 1054 to provide therapy to the brain basedon a cardiac or respiratory detection. Once therapy has been initiatedfrom a cardiac/respiratory detection, the device monitors the amount oftime therapy has been delivered at block 1056. This time period isprogrammable. The processor continues to receive a brain signal at block1058. At decision block 1060 the processor determines when theprogrammed time period has been exceeded without detection of aneurological event in the brain signal. If the answer is “Yes” (i.e.,the cardiac or respiratory initiated brain therapy has been ongoing forthe programmed time period without the occurrence of a neurologicalevent in the brain signal), then therapy to the brain is discontinued atblock 1062. If the patient has entered a neurological event whilereceiving cardiac/respiratory initiated therapy, control of therapy istransferred to the monitoring of the brain by the neurological eventdetection algorithm, and therapy decisions are made using the brainsignals at block 1064. At this point therapy may continue until the EEGdetection algorithm determines that the neurological event has ended.Then therapy may be terminated based on the detected end of theneurological event based on the EEG detection algorithm output.

FIG. 40A discussed above shows a process 971 for determining whether toenable the cardiac or respiratory detectors for neurological eventdetection and treatment. Once the cardiac or respiratory signals havebeen enabled for neurological event detection monitoring and treatmentat block 986 and the neurological event detection algorithm has beenenabled for modulation or other input into cardiac or respiratorytherapy, the cardiac/respiratory parameters for ictal/post-ictaltreatment options are defined at block 987. At block 988,cardiac/respiratory events to treat when in a neurological state aredefined. At block 989, cardiac/respiratory events to treat when outsidea neurological event are defined. At block 990, therapy terminationconditions (i.e., turn over control of brain therapy to the neurologicalevent detection algorithm and terminate if a neurological event is notentered in a programmable period of time) are defined and the monitorstarts monitoring or treatment at block 985.

If the matching test of the flow diagram of FIG. 40A shows that one typeof cardiac event (type 1) is associated with neurological event onsetwhile other types of cardiac events (type 2) occur frequently, but haveno temporal relationship to the neurological event, then the physicianmay chose to direct therapy to the Brain (or Brain and Heart) upon type1 event detection or direct therapy to the Heart on type 2 detection.

In the present invention as described in relation to the devices shownabove in FIGS. 11-25 and 41-55, the physician is able to selectivelychoose which cardiac and respiratory events to treat in seizure andnon-seizure states. For example, the device may be programmed to treatincidences of tachycardia in non-seizure states, but not in seizurestates, where this type of cardiac behavior is expected and considerednormal. Also, the patient may experience certain ECG or respiratoryabnormalities, which are seizure induced, but cause no complications orincreased health risk to the patient. In such cases, the physician maydecide to suppress treatment for these events if detected during aseizure. This cannot be accomplished with existing pacemaker technology,which operates on ECG signals only.

There are other instances in which a detected ECG or respiratoryabnormality does pose a health risk, regardless of when it occurs andhow it was induced. For these events, the physician may choose a mode ofoperation that treats the ECG/respiratory abnormality in both seizureand non-seizure states (i.e., asystole, apnea).

Additionally, the physician may choose to treat the same ECG/respiratoryevent in both seizure and non-seizure states, but may define differentthresholds (i.e., duration or intensity) for treating the event. Forexample, during a seizure state, a higher heart rate or sustainedoccurrence of tachycardia may be required before cardiac treatment isinitiated, relative to a non-seizure state. This feature would enablecardiac therapy during status epilepticus, which is a prolongedcondition, but suppress it for typical seizure behaviors.

If the matching test of the flow diagram of FIG. 57 shows that the ECGor respiratory signals do not improve seizure detection, but patient isat cardiac risk, the physician may choose to enable the ECG/respiratorydetector to deliver therapy to the heart or diaphragm.

If the matching test of the flow diagram of FIG. 57 shows that the ECGor respiratory signals improves seizure detection, but the patient isalso at cardiac risk, the physician may choose to treat the brain (forseizures) with EEG, ECG or respiratory detection, and heart (for cardiacproblems) with ECG detection.

Preventative Pacing Therapy

Optionally, the therapy systems of FIGS. 11-25 and 41-55 may also havepre-emptive or preventative pacing capabilities. For example, upon EEGdetection of seizure onset or imminent seizure onset, the pacing systemsdescribed in conjunction with FIGS. 11-25 and 41-55 may beginpreventative overdrive pacing to prevent or mitigate sleep apnea such asdescribed in U.S. Pat. No. 6,126,611 “Apparatus for Management of SleepApnea” to Bourgeois. The '611 patent detects sleep apnea and begins topace the heart at a rate of 70-100 PPM (overdrive pacing the sleepintrinsic rate of typically 30-55 BPM) causing arousal andelimination/prevention of sleep apnea. The herein described inventionuses the detection of the onset or impending onset of a seizure totrigger sleep apnea overdrive pacing to preemptively prevent theinitiation of apnea. Upon the sensing of seizure termination or apreprogrammed timeout, the sleep apnea prevention overdrive pacing isterminated/inactivated.

Alternatively, the pacing systems may begin ventricular pacing overdriveupon sensing a ventricular premature contraction to prevent theinitiation of ventricular arrhythmias such as described in U.S. Pat. No.4,503,857 “Programmable Cardiac Pacemaker with Microprocessor Control ofPacer Rate” to Boute, et al and U.S. Pat. No. 5,312,451 “Apparatus andMethods for Controlling a Cardiac Pacemaker in the Event of aVentricular Extrasystole” to Limousin, et al. Upon detection of theonset or impending onset of a seizure ventricular extrasystole overdrivepacing may be initiated, and subsequent to the programmed number ofcycles, a slowing of the ventricular rate until either the programmedbase rate is reached or a sinus detection occurs. Upon the sensing ofseizure termination or a preprogrammed timeout, the sleep apneaprevention overdrive pacing is terminated/inactivated.

Additionally, the pacing systems described in conjunction with FIGS.11-25 and 41-55 may include AF preventative pacing therapies asdescribed in U.S. Pat. No. 6,185,459 “Method and Apparatus forPrevention of Atrial Tachyarrhythmias” to Mehra, et al or U.S. Pat. No.6,650,938 Method and System for Preventing Atrial Fibrillation by RapidPacing Intervention” to Boute. The '459 and “938 patents describesystems that sense premature atrial events and initiate overdrive pacingalgorithms to prevent the initiation of atrial arrhythmias. In thepresent invention, upon detection of the onset or impending onset of aseizure, ventricular extrasystole AF overdrive pacing may be initiated,and subsequent to the programmed number of cycles, a slowing of theventricular rate until either the programmed base rate is reached or asinus detection occurs. Upon the sensing of seizure termination or apreprogrammed timeout, the sleep apnea prevention overdrive pacing isterminated/inactivated.

Signal Processing

The signal processing of cardiac, respiration or electroencephalogramsignals of the above-described embodiments may include analog,continuous wave bandpass filtering as is well known in the art.Additionally, digital signal processing techniques as substantiallydescribed in U.S. Pat. No. 6,029,087 “Cardiac Pacing System withImproved Physiological Event Classification Based Upon DSP” toWohlgemuth and U.S. Pat. No. 6,556,859 “System and Method forClassifying Sensed Atrial Events in a Cardiac Pacing System” toWohlgemuth, et al may be used. Additionally, fuzzy logic processingtechniques as described in U.S. Pat. No. 5,626,622 “Dual Sensor RateResponsive Pacemaker” to Cooper and U.S. Pat. No. 5,836,988 “RateResponsive Pacemaker with Exercise Recovery Using Minute VolumeDetermination” to Cooper, et al. may be used to determine/detect theoccurrence or onset of seizures, respiratory or cardiac anomalies.

The devices of the above-described systems that contain 2 individualunits in 2-way communication (e.g., the systems of FIG. 20-23) mayoptionally transmit events via the communication channel by one ofseveral ways including, but not limited to, individual event logicsignal, marker channel or processed signal.

Power Saving and Clock Synchronization

The devices of the above-described systems that contain 2 individualunits in 2-way communication (e.g., the systems of FIG. 20-23, 43,45-47, 49, 52, 53, 55) may optionally have a reduced power capabilityduring communication. The devices may communicate at a predefinedspecific time interval with clocks in each unit of the systemupdated/resynchronized on each communication (as described in U.S. Pat.No. 6,083,248 “World Wide Patient Location and Data Telemetry System forImplantable Medical Devices” to Thompson. Optionally, a receiving unitmay open a window at a period interval (e.g., 1 second) for a briefwindow (e.g., 100 mSec) to look for an incoming transmission from theother system unit.

Drug Pump

The therapy device in above devices as described in systems as describedin conjunction with FIGS. 11-25 and 41-55 may optionally contain a drugpump to deliver liquid medicants in lieu of stimulation or incombination with stimulation. Medicants used could include epilepticdrugs (examples of such drugs include, but are not limited tointrathecal delivery of CGX-1007 or Baclofen), mental health and mooddisorder related drugs, cardiac drugs (examples of such drugs include,but are not limited to, pharmaceutical compositions comprisingbeta-adrenergic blocking agents, protain emide, type 1 antiarrhythmicagents such as disopyramide, class II agents such as propafenone,alphaagonists such as ephedrine and midodrine, and other antiarrhymicagents such as amiodarone, and combinations thereof) or respiratorydrugs (examples of such drugs include, but are not limited todiuretics).

Remote Monitoring

The present invention also allows the residential, hospital orambulatory monitoring of at-risk patients and their implanted medicaldevices at any time and anywhere in the world (see system 900 FIG. 58).Medical support staff 906 at a remote medical support center 914 mayinterrogate and read telemetry from the implanted medical device andreprogram its operation while the patient 10 is at very remote or evenunknown locations anywhere in the world. Two-way voice communications910 via satellite 904, cellular via link 32 or land lines 956 with thepatient 10 and data/programming communications with the implantedmedical device 958 via a belt worn transponder 960 may be initiated bythe patient 10 or the medical support staff 906. The location of thepatient 10 and the implanted medical device 958 may be determined viaGPS 902 and link 908 and communicated to the medical support network inan emergency. Emergency response teams can be dispatched to thedetermined patient location with the necessary information to preparefor treatment and provide support after arrival on the scene. See forexample, U.S. Pat. No. 5,752,976 “World Wide Patient Location and DataTelemetry System for Implantable Medical Devices” to Duffin et al.

An alternative or addition to the remote monitoring system as describedabove in conjunction with FIG. 58 is shown in the system 950 of FIG. 59,which shows a patient 10 sleeping with an implantable Monitor 958 oroptional therapy device as described above in connection with thesystems of FIG. 1-57. The implantable device 958, upon detection of aneurological event (such as a seizure), respiratory apnea or cardiacconduction anomaly (ie, heart rate variability, QT extension,arrhythmia) may alert a remote monitoring location via local remote box952 (as described in U.S. Pat. No. 5,752,976 “World Wide PatientLocation and Data Telemetry System for Implantable Medical Devices” toDuffin, et al.) telephone 954 and phone lines 956 or the patient's careprovider via an RF link 32 to a pager-sized remote monitor 960 placed inother locations in the house or carried (ie, belt worn) by the careprovider 962. The remote caregiver monitor 960 may include audiblebuzzes/tones/beeps, vocal, light or vibration to alert the caregiver 962of patient's monitor in an alarm/alert condition. The RF link mayinclude RF portable phone frequencies, power line RF links, HomeRF,Bluetooth, ZigBee, WIFI, MICS band (medical implant communicationsservice), or any other interconnect methods as appropriate. Often thecare provider 962 may be able to take some action to help the patient10. For example, the care provider may arouse the patient 10 from aneurological event (such as a SUDEP episode) by shaking them, arousingthem, reposition the patient, or the like.

Patient Alert

The monitor (and optionally therapy) devices as described in systemsdescribed above in conjunction with FIG. 1-57 may optionally allow apatient alert to allow the patient an early warning of impendingseizure, respiratory or cardiac anomalies via vibration (e.g., piezobuzzer in implanted device, a vibrator as used in a cell phone or pagerin a “silent ring” mode in vest, patch or patient activator), audiblebuzzing or tones (e.g., audible in cranial implant, audible via externalpatch, patient activator or vest), light (e.g., external vest or patientactivator) or vocal (e.g., spoken word in cranial, vest, external patch,or patient activator) indicators of the monitor in an alarm/alertcondition.

It will be apparent from the foregoing that while particular embodimentsof the invention have been illustrated and described, variousmodifications can be made without departing from the spirit and scope ofthe invention. Accordingly, it is not intended that the invention belimited, except as by the appended claims.

What is claimed is:
 1. A medical device system comprising: (a) a brainmonitoring element for sensing activity in the brain and outputting abrain signal; (b) a respiratory monitoring element for sensing activityin the respiratory system and outputting a respiratory signal; (c) atherapy module for providing therapeutic output to a brain; and (d) aprocessor in communication with the brain monitoring element, therespiratory monitoring element and the therapy module, the processorconfigured to perform the following: (i) detecting a respiratory eventin the respiratory signal; (ii) activating the therapy module to providethe therapeutic output to the brain based on detecting a respiratoryevent; (iii) monitoring the brain signal for an activity indicative of anervous system disorder; (iv) determining whether an activity indicativeof a nervous system disorder has been detected in the brain signalwithin a specified period of time after detection of the respiratoryevent in the respiratory signal; and (v) communicating to the therapymodule to change the therapeutic output to the brain based upon themonitoring of the brain signal.
 2. The medical device system of claim 1wherein the therapeutic output is provided through the brain monitoringelement.
 3. The medical device system of claim 1 wherein monitoring thebrain signal comprises execution of a neurological event detectionalgorithm that outputs an indication that a neurological event isoccurring or is not occurring based on an evaluation of the brainsignal.
 4. The medical device system of claim 3 wherein the processor isfurther configured to determine when a period of time has passed afterdetection of the respiratory event in the respiratory signal withoutdetection of a neurological event in the brain signal.
 5. The medicaldevice system of claim 4 wherein the processor is further configured todiscontinue the therapeutic output to the brain when the period of timehas passed without detection of a neurological event in the brainsignal.
 6. The medical device system of claim 4 wherein the period oftime is programmable.
 7. The medical device system of claim 4 whereinthe period of time is set at less than 10 minutes.
 8. The medical devicesystem of claim 4 wherein the period of time is set at less than 5minutes.
 9. The medical device system of claim 4 wherein the period oftime is set at less than 2 minutes.
 10. The medical device of claim 3wherein the step of detecting a neurological event further comprisesdetecting an end of the neurological event, and wherein communicating tothe therapy module to change the therapeutic output to the braincomprises discontinuing the therapeutic output to the brain based uponthe detecting the end of the neurological event.
 11. The medical deviceof claim 1 further comprising a body implantable housing, the housingcontaining the therapy module and the processor.
 12. A medical devicesystem of claim 1 further comprising a cardiac monitoring element forsensing activity in the heart and outputting a cardiac signal, andwherein the processor is further configured to detect a cardiac event inthe cardiac signal, and wherein the step of activating the therapymodule to provide the therapeutic output to the brain based on detectinga respiratory event comprises activating the therapy module to provide atherapeutic output to the brain based on detecting a respiratory eventor a cardiac event.
 13. A medical device system comprising: (a) a brainmonitoring element for sensing activity in the brain and outputting abrain signal; (b) a respiratory monitoring element for sensing activityin the respiratory system and outputting a respiratory signal; (c)therapy means for providing therapeutic output to a brain; and (d)control means in communication with the brain monitoring element, therespiratory monitoring element and the therapy means, the control meanscomprising: (i) respiratory detection means for detecting a respiratoryevent and providing a respiratory detection output; (ii) activationmeans for activating the therapy module to provide therapy to the brainbased upon the respiratory detection output; (iii) brain monitor meansfor evaluating the brain signal for an activity indicative of a nervoussystem disorder and providing a brain monitoring output; (iv)determination means for determining whether an activity indicative of anervous system disorder has been detected in the brain signal within aspecified period of time after detection of the respiratory event in therespiratory signal; and (v) communication means for informing thetherapy module to change the therapy to the brain based upon the brainmonitoring output.
 14. A medical device system comprising: (a) a brainmonitoring element for sensing activity in the brain and outputting abrain signal; (b) a respiratory monitoring element for sensing activityin the respiratory system and outputting a respiratory signal; (c) atherapy module for providing therapeutic output to a brain; and (d) aprocessor in communication with the brain monitoring element, therespiratory monitoring element and the therapy module, the processorconfigured to perform the following: (i) detecting a respiratory eventin the respiratory signal; (ii) activating the therapy module to providethe therapeutic output to the brain based on detecting a respiratoryevent; (iii) initiating monitoring the brain signal after detecting therespiratory event; and (iv) communicating to the therapy module tochange the therapeutic output to the brain based upon the monitoring ofthe brain signal.